UniProtKB/Swiss-Prot P29033: Variant p.Val37Ile

Gap junction beta-2 protein
Gene: GJB2
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Variant information Variant position:

37 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Valine (V) to Isoleucine (I) at position 37 (V37I, p.Val37Ile). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In DFNB1A. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs72474224 [ dbSNP | Ensembl ]

Sequence information Variant position:

37 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

226 The length of the canonical sequence.
Location on the sequence:

STSIGKIWLTVLFIFRIMIL V VAAKEVWGDEQADFVCNTLQ The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Gorilla                       STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Rhesus macaque                STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Mouse                         STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Rat                           STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Bovine                        STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Sheep                         STSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQ

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 226	Gap junction beta-2 protein
Transmembrane	21 – 40	Helical
Binding site	42 – 42	in other chain
Binding site	45 – 45
Binding site	47 – 47
Mutagenesis	34 – 34	M -> A. Loss of gap junction ion conductance, probably due to very low open probability of the channels. Can form functional channels with wild-type, but with strongly reduced channel conductance. No visible effect on channel assembly and membrane insertion.
Helix	19 – 38

Literature citations
Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants.
Gasmelseed N.M.A.; Schmidt M.; Magzoub M.M.A.; Macharia M.; Elmustafa O.M.; Ototo B.; Winkler E.; Ruge G.; Horstmann R.D.; Meyer C.G.;
Hum. Mutat. 23:206-207(2004)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT DFNB1A ILE-37; VARIANTS 46-ASP--GLN-48 DELINS GLU; HIS-127; ILE-153; SER-160 AND MET-167; Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.
Kelley P.M.; Harris D.J.; Comer B.C.; Askew J.W.; Fowler T.; Smith S.D.; Kimberling W.J.;
Am. J. Hum. Genet. 62:792-799(1998)
Cited for: VARIANTS DFNB1A LEU-84; MET-95 AND ARG-113; VARIANTS ILE-27 AND ILE-37; Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population.
Kudo T.; Ikeda K.; Kure S.; Matsubara Y.; Oshima T.; Watanabe K.; Kawase T.; Narisawa K.; Takasaka T.;
Am. J. Med. Genet. 90:141-145(2000)
Cited for: VARIANTS ILE-27; ILE-37; GLY-114 AND THR-203; High frequency hearing loss correlated with mutations in the GJB2 gene.
Wilcox S.A.; Saunders K.; Osborn A.H.; Arnold A.; Wunderlich J.; Kelly T.; Collins V.; Wilcox L.J.; McKinlay Gardner R.J.; Kamarinos M.; Cone-Wesson B.; Williamson R.; Dahl H.-H.M.;
Hum. Genet. 106:399-405(2000)
Cited for: VARIANTS DFNB1A ILE-37; PRO-90 AND TRP-184; Homozygosity for the V37I Connexin 26 mutation in three unrelated children with sensorineural hearing loss.
Bason L.; Dudley T.; Lewis K.; Shah U.; Potsic W.; Ferraris A.; Fortina P.; Rappaport E.; Krantz I.D.;
Clin. Genet. 61:459-464(2002)
Cited for: VARIANT DFNB1A ILE-37; A novel dominant missense mutation -- D179N -- in the GJB2 gene (connexin 26) associated with non-syndromic hearing loss.
Primignani P.; Castorina P.; Sironi F.; Curcio C.; Ambrosetti U.; Coviello D.A.;
Clin. Genet. 63:516-521(2003)
Cited for: VARIANT DFNA3A ASN-179; VARIANT DFNB1A ILE-37; GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation.
Ohtsuka A.; Yuge I.; Kimura S.; Namba A.; Abe S.; Van Laer L.; Van Camp G.; Usami S.;
Hum. Genet. 112:329-333(2003)
Cited for: VARIANTS DEAFNESS GLU-45; THR-71; ARG-86 AND TRP-143; VARIANTS ILE-27; ILE-37; GLY-114; ASN-123; LEU-191 AND THR-203; M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance.
Pollak A.; Skorka A.; Mueller-Malesinska M.; Kostrzewa G.; Kisiel B.; Waligora J.; Krajewski P.; Oldak M.; Korniszewski L.; Skarzynski H.; Ploski R.;
Am. J. Med. Genet. A 143:2534-2543(2007)
Cited for: VARIANTS DFNB1A THR-34 AND ILE-37; Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss.
Riahi Z.; Hammami H.; Ouragini H.; Messai H.; Zainine R.; Bouyacoub Y.; Romdhane L.; Essaid D.; Kefi R.; Rhimi M.; Bedoui M.; Dhaouadi A.; Feldmann D.; Jonard L.; Besbes G.; Abdelhak S.;
Gene 525:1-4(2013)
Cited for: VARIANTS DFNB1A ILE-37 AND ALA-130; Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel.
Shen J.; Oza A.M.; Del Castillo I.; Duzkale H.; Matsunaga T.; Pandya A.; Kang H.P.; Mar-Heyming R.; Guha S.; Moyer K.; Lo C.; Kenna M.; Alexander J.J.; Zhang Y.; Hirsch Y.; Luo M.; Cao Y.; Wai Choy K.; Cheng Y.F.; Avraham K.B.; Hu X.; Garrido G.; Moreno-Pelayo M.A.; Greinwald J.; Zhang K.; Zeng Y.; Brownstein Z.; Basel-Salmon L.; Davidov B.; Frydman M.; Weiden T.; Nagan N.; Willis A.; Hemphill S.E.; Grant A.R.; Siegert R.K.; DiStefano M.T.; Amr S.S.; Rehm H.L.; Abou Tayoun A.N.;
Genet. Med. 21:2442-2452(2019)
Cited for: CONFIRMED PATHOGENICITY OF VARIANTS DFNB1A THR-34 AND ILE-37;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.