NM_000222.3(KIT):c.1471T>C (p.Cys491Arg) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 22, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001296683.8

Allele description [Variation Report for NM_000222.3(KIT):c.1471T>C (p.Cys491Arg)]

NM_000222.3(KIT):c.1471T>C (p.Cys491Arg)

Gene:

KIT:KIT proto-oncogene, receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_000222.3(KIT):c.1471T>C (p.Cys491Arg)

HGVS:

NC_000004.12:g.54725981T>C
NG_007456.1:g.72987T>C
NM_000222.3:c.1471T>CMANE SELECT
NM_001093772.2:c.1471T>C
NM_001385284.1:c.1474T>C
NM_001385285.1:c.1471T>C
NM_001385286.1:c.1471T>C
NM_001385288.1:c.1474T>C
NM_001385290.1:c.1474T>C
NM_001385292.1:c.1474T>C
NP_000213.1:p.Cys491Arg
NP_001087241.1:p.Cys491Arg
NP_001372213.1:p.Cys492Arg
NP_001372214.1:p.Cys491Arg
NP_001372215.1:p.Cys491Arg
NP_001372217.1:p.Cys492Arg
NP_001372219.1:p.Cys492Arg
NP_001372221.1:p.Cys492Arg
LRG_307:g.72987T>C
NC_000004.11:g.55592147T>C

Protein change:

C491R

Links:

dbSNP: rs1722194127

NCBI 1000 Genomes Browser:

rs1722194127

Molecular consequence:

NM_000222.3:c.1471T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1471T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1474T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1471T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1471T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1474T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1474T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1474T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001485654	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 22, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001485654

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 22, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001485654.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has not been reported in the literature in individuals with KIT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 491 of the KIT protein (p.Cys491Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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