UniProtKB/Swiss-Prot P24928: Variant p.Met769Thr

DNA-directed RNA polymerase II subunit RPB1
Gene: POLR2A
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Variant information Variant position:

769 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 Methionine (M) to Threonine (T) at position 769 (M769T, p.Met769Thr). 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 (M) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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 NEDHIB; uncertain significance; severe. Any additional useful information about the variant.

Sequence information Variant position:

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

1970 The length of the canonical sequence.
Location on the sequence:

RDKTGSSAQKSLSEYNNFKS M VVSGAKGSKINISQVIAVVG 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                         RDKTGSSAQKSLSEYNNFKSMVVSGAKGSKINISQVIAVVG

Mouse                         RDKTGSSAQKSLSEYNNFKSMVVSGAKGSKINISQVIAVVG

Caenorhabditis elegans        RDRTGSSAQKSLSEFNNFKSMVVSGSKGSKINISQVIACVG

Drosophila                    RDKTGGSAKKSLTEYNNLKAMVVSGSKGSNINISQVIACVG

Slime mold                    RDTAGSSAQDSLSEDNNLKAMVTAGSKGSFINISQMMACVG

Baker's yeast                 RDKAGRLAEVNLKDLNNVKQMVMAGSKGSFINIAQMSACVG

Fission yeast                 RDNAGRSAEHSLKDSNNVKQMVAAGSKGSFINISQMSACVG

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 – 1970	DNA-directed RNA polymerase II subunit RPB1
Alternative sequence	567 – 1970	Missing. In isoform 2.

Literature citations
De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia.
Haijes H.A.; Koster M.J.E.; Rehmann H.; Li D.; Hakonarson H.; Cappuccio G.; Hancarova M.; Lehalle D.; Reardon W.; Schaefer G.B.; Lehman A.; van de Laar I.M.B.H.; Tesselaar C.D.; Turner C.; Goldenberg A.; Patrier S.; Thevenon J.; Pinelli M.; Brunetti-Pierri N.; Prchalova D.; Havlovicova M.; Vlckova M.; Sedlacek Z.; Lopez E.; Ragoussis V.; Pagnamenta A.T.; Kini U.; Vos H.R.; van Es R.M.; van Schaik R.F.M.A.; van Essen T.A.J.; Kibaek M.; Taylor J.C.; Sullivan J.; Shashi V.; Petrovski S.; Fagerberg C.; Martin D.M.; van Gassen K.L.I.; Pfundt R.; Falk M.J.; McCormick E.M.; Timmers H.T.M.; van Hasselt P.M.;
Am. J. Hum. Genet. 105:283-301(2019)
Cited for: INVOLVEMENT IN NEDHIB; VARIANTS NEDHIB LEU-371; THR-457; SER-531; TYR-669 DEL; 700-GLN--ASN-1970 DEL; 735-GLN--ASN-1970 DEL; MET-736; SER-755 DEL; THR-769; THR-848; HIS-1109; PRO-1124; LYS-1125 DEL; SER-1251 AND HIS-1603; CHARACTERIZATION OF VARIANTS NEDHIB THR-457; SER-531; MET-736; SER-755 DEL; PRO-1124; SER-1251 AND HIS-1603; MUTAGENESIS OF 812-LYS--ASN-1970;

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.