UniProtKB/Swiss-Prot Q13315: Variant p.Tyr1961Cys

Serine-protein kinase ATM
Gene: ATM
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Variant information Variant position:

1961 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 Tyrosine (Y) to Cysteine (C) at position 1961 (Y1961C, p.Tyr1961Cys). 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 large size and aromatic (Y) to medium size and polar (C) 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:

Found in a patient with familial pancreatic cancer; uncertain significance; also found in a lung adenocarcinoma sample; uncertain significance; decreased phosphorylation of target proteins. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs56399311 [ dbSNP | Ensembl ]

Sequence information Variant position:

1961 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

3056 The length of the canonical sequence.
Location on the sequence:

VAKVAQSCAAHFTALLYAEI Y ADKKSMDDQEKRSLAFEEGS 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                         VAKVAQSCAAH-FTALLYAEIYADKKSMDDQEK--RSLAFEEGS

Mouse                         VAKVAQSCSAH-FTALLYAEIYSDKKSTDEQEK--RSPTFE

Pig                           VAKVAQSCAAH-FTALLYAEIYADKKNMDDQEK--RSPTFE

Caenorhabditis elegans        FLKHGFTTHSFAIANILFDRLSARKRNTMMIDR--------

Drosophila                    VVMASNHCQAY-FLSIMYLELWACSESPKSKADFLDNECFQ

Baker's yeast                 ICQISLKIKEFKFGYLLFEEMNMPNIREMNINT--------

Fission yeast                 AASTAYDCHLY-EQSLLFLTIHNTKTDELDITL--------

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	2 – 3056	Serine-protein kinase ATM
Domain	1940 – 2566	FAT
Modified residue	1981 – 1981	Phosphoserine; by autocatalysis
Mutagenesis	1941 – 1941	V -> L. Decreased phosphorylation of target proteins.
Mutagenesis	1981 – 1981	S -> A. Loss of IR-induced S-1981 autophosphorylation. Reduced correction of cell cycle checkpoint defects and DNA-repair activity. No effect on S-367 nor S-1893 autophosphorylation. No dimer disruption.
Mutagenesis	1981 – 1981	S -> DE. Disrupts the dimer.
Helix	1951 – 1973

Literature citations
Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-23; CYS-49; GLU-126; HIS-140; GLN-250; PHE-333; CYS-337; HIS-337; ALA-410; SER-504; ASP-514; TYR-540; VAL-546; LEU-582; PRO-707; GLN-848; LEU-858; SER-872; TRP-924; ALA-935; ARG-1054; PHE-1179; ILE-1321; TYR-1380; SER-1382; PHE-1420; MET-1469; CYS-1475; SER-1650; THR-1739; ASN-1853; VAL-1853; ILE-1916; THR-1945; CYS-1961; ASP-1991; PHE-2307; PRO-2332; PHE-2356; LEU-2408; PRO-2442; GLN-2443; ARG-2464; ARG-2492; ALA-2666; HIS-2719; ARG-2842 AND ASN-2870; Modeling ATM mutant proteins from missense changes confirms retained kinase activity.
Barone G.; Groom A.; Reiman A.; Srinivasan V.; Byrd P.J.; Taylor A.M.;
Hum. Mutat. 30:1222-1230(2009)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS AT LEU-292; PRO-1465; ILE-1743; THR-2274; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; ASP-2554; GLY-2668; CYS-2827; 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008; CHARACTERIZATION OF VARIANTS VAL-546; ARG-1054; ILE-1322; ARG-1691; CYS-1961 AND SER-2765; VARIANT ILE-1322; MUTAGENESIS OF LYS-1807; VAL-1941; TYR-2019; GLU-2039; LEU-2338; SER-2394; LEU-2452; SER-2685; PRO-2699; ASP-2708 AND GLN-2730; Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.
Chaffee K.G.; Oberg A.L.; McWilliams R.R.; Majithia N.; Allen B.A.; Kidd J.; Singh N.; Hartman A.R.; Wenstrup R.J.; Petersen G.M.;
Genet. Med. 20:119-127(2018)
Cited for: VARIANTS VAL-68; ILE-341; LEU-597; GLY-699; GLY-759; SER-813; GLY-869; ILE-897; ASP-1474; VAL-1488; CYS-1961; ALA-2287; PHE-2307; ARG-2464; PRO-2524; THR-2531; GLN-2810; HIS-2832; LEU-2974; ASP-3029 AND LEU-3056;

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.