NM_000222.3(KIT):c.1951A>T (p.Met651Leu) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 2023
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:: RCV000458431.11

Allele description [Variation Report for NM_000222.3(KIT):c.1951A>T (p.Met651Leu)]

NM_000222.3(KIT):c.1951A>T (p.Met651Leu)

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.1951A>T (p.Met651Leu)

HGVS:

NC_000004.12:g.54728082A>T
NG_007456.1:g.75088A>T
NM_000222.3:c.1951A>TMANE SELECT
NM_001093772.2:c.1939A>T
NM_001385284.1:c.1954A>T
NM_001385285.1:c.1951A>T
NM_001385286.1:c.1939A>T
NM_001385288.1:c.1942A>T
NM_001385290.1:c.1954A>T
NM_001385292.1:c.1942A>T
NP_000213.1:p.Met651Leu
NP_000213.1:p.Met651Leu
NP_001087241.1:p.Met647Leu
NP_001372213.1:p.Met652Leu
NP_001372214.1:p.Met651Leu
NP_001372215.1:p.Met647Leu
NP_001372217.1:p.Met648Leu
NP_001372219.1:p.Met652Leu
NP_001372221.1:p.Met648Leu
LRG_307t1:c.1951A>T
LRG_307:g.75088A>T
LRG_307p1:p.Met651Leu
NC_000004.11:g.55594248A>T
NM_000222.2:c.1951A>T

Protein change:

M647L

Links:

dbSNP: rs534209826

NCBI 1000 Genomes Browser:

rs534209826

Molecular consequence:

NM_000222.3:c.1951A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1939A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1954A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1951A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1939A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1942A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1954A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1942A>T - 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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PREDICTED: Oryza sativa Japonica Group beta-1,3-galactosyltransferase GALT1 (LOC...
PREDICTED: Oryza sativa Japonica Group beta-1,3-galactosyltransferase GALT1 (LOC4340564), mRNA
gi|2756268419|ref|XM_015788359.3|

Nucleotide
Similar studies for GEO DataSets (Select 200112986) (6)
GEO DataSets
GSE64036[ACCN] AND gsm[ETYP] (2)
GEO DataSets
GSE85760[ACCN] AND gsm[ETYP] (7)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550103	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 19, 2023)	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

SCV000550103

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 19, 2023)

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, SCV000550103.8

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 651 of the KIT protein (p.Met651Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 409763). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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: Oct 13, 2024

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