UniProtKB/Swiss-Prot O43511: Variant p.Leu445Trp

Pendrin
Gene: SLC26A4
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Variant information Variant position:

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

US 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 Leucine (L) to Tryptophan (W) at position 445 (L445W, p.Leu445Trp). 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:

Change from medium size and hydrophobic (L) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 PDS and DFNB4; uncertain significance; also found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs111033307 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

IISAAIVMIAILALGKLLEP L QKSVLAAVVIANLKGMFMQL 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                         IISAAIVMIAILALGKLLEPLQKSVLAAVVIANLKGMFMQL

Mouse                         LISAVIVMVAIVALGRLLEPLQKSVLAAVVIANLKGMFMQV

Rat                           LISAVIVMVAIVALGKLLEPLQKSVLAAVVIANLKGMFMQV

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 – 780	Pendrin
Topological domain	443 – 448	Cytoplasmic

Literature citations
Two frequent missense mutations in Pendred syndrome.
van Hauwe P.; Everett L.A.; Coucke P.; Scott D.A.; Kraft M.L.; Ris-Stalpers C.; Bolder C.; Otten B.; de Vijlder J.J.M.; Dietrich N.L.; Ramesh A.; Srisailapathy S.C.R.; Parving A.; Cremers C.W.R.J.; Willems P.J.; Smith R.J.H.; Green E.D.; van Camp G.;
Hum. Mol. Genet. 7:1099-1104(1998)
Cited for: VARIANTS PDS PHE-138; ALA-139; VAL-209; PRO-236; HIS-271; HIS-409; PRO-416; TRP-445; TYR-565 AND ARG-723; Pendred syndrome: phenotypic variability in two families carrying the same PDS missense mutation.
Masmoudi S.; Charfedine I.; Hmani M.; Grati M.; Ghorbel A.M.; Elgaied-Boulila A.; Drira M.; Hardelin J.-P.; Ayadi M.;
Am. J. Med. Genet. 90:38-44(2000)
Cited for: VARIANT PDS TRP-445; Enlarged vestibular aqueduct: a radiological marker of Pendred syndrome, and mutation of the PDS gene.
Reardon W.; O'Mahoney C.F.; Trembath R.; Jan H.; Phelps P.D.;
QJM 93:99-104(2000)
Cited for: VARIANTS DFNB4 PHE-117; VAL-209; PRO-236; MET-410; PRO-416; TRP-445 AND ARG-446; Identification of five new mutations of PDS/SLC26A4 in Mediterranean families with hearing impairment.
Lopez-Bigas N.; Melchionda S.; de Cid R.; Grifa A.; Zelante L.; Govea N.; Arbones M.L.; Gasparini P.; Estivill X.;
Hum. Mutat. 18:548-548(2001)
Cited for: VARIANTS PDS TRP-445; HIS-556 AND MET-721; VARIANTS DFNB4 ILE-132 AND MET-410; Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations.
Prasad S.; Koelln K.A.; Cucci R.A.; Trembath R.C.; Van Camp G.; Smith R.J.H.;
Am. J. Med. Genet. A 124:1-9(2004)
Cited for: VARIANTS PDS/DFNB4 GLY-24; GLN-29; CYS-78; VAL-104; CYS-105; ASP-106; PHE-138; ALA-139; VAL-209; PRO-236; HIS-271; LEU-335; GLY-384; HIS-409; MET-410; PRO-416; ARG-421; ALA-429 DEL; TRP-445; ASP-480; HIS-530; CYS-556; TYR-565; ALA-653; GLU-672; SER-683 AND ARG-723; VARIANTS TYR-324 AND SER-597; Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.
Blons H.; Feldmann D.; Duval V.; Messaz O.; Denoyelle F.; Loundon N.; Sergout-Allaoui A.; Houang M.; Duriez F.; Lacombe D.; Delobel B.; Leman J.; Catros H.; Journel H.; Drouin-Garraud V.; Obstoy M.-F.; Toutain A.; Oden S.; Toublanc J.E.; Couderc R.; Petit C.; Garabedian E.-N.; Marlin S.;
Clin. Genet. 66:333-340(2004)
Cited for: VARIANTS PDS GLN-29; CYS-78; PRO-137; PHE-138; ILE-193; VAL-209; PRO-236; ASN-391; HIS-409; MET-410; PRO-416; TRP-445; HIS-530; ILE-552; PRO-694; MET-721 AND ASN-724; VARIANT SER-597; Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?
Choi B.Y.; Stewart A.K.; Madeo A.C.; Pryor S.P.; Lenhard S.; Kittles R.; Eisenman D.; Kim H.J.; Niparko J.; Thomsen J.; Arnos K.S.; Nance W.E.; King K.A.; Zalewski C.K.; Brewer C.C.; Shawker T.; Reynolds J.C.; Butman J.A.; Karniski L.P.; Alper S.L.; Griffith A.J.;
Hum. Mutat. 30:599-608(2009)
Cited for: VARIANTS PDS PHE-138; VAL-209; PRO-236; GLY-384; MET-402; PRO-416; TRP-445; ARG-514; HIS-530; TYR-565 AND THR-775; VARIANTS DFNB4 LEU-335; MET-402; SER-530 AND THR-775; VARIANTS SER-597; GLY-609 AND CYS-776; Use of SLC26A4 mutation testing for unilateral enlargement of the vestibular aqueduct.
Chattaraj P.; Reimold F.R.; Muskett J.A.; Shmukler B.E.; Chien W.W.; Madeo A.C.; Pryor S.P.; Zalewski C.K.; Butman J.A.; Brewer C.C.; Kenna M.A.; Alper S.L.; Griffith A.J.;
JAMA Otolaryngol. Head Neck Surg. 139:907-913(2013)
Cited for: VARIANTS DFNB4 THR-185; LEU-335 AND THR-775; VARIANTS LEU-335; GLY-384; TRP-445; SER-597 AND CYS-776; CHARACTERIZATION OF VARIANT DFNB4 THR-185; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION;

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.