NM_000222.3(KIT):c.1373A>T (p.Asp458Val) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000633836.10

Allele description [Variation Report for NM_000222.3(KIT):c.1373A>T (p.Asp458Val)]

NM_000222.3(KIT):c.1373A>T (p.Asp458Val)

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.1373A>T (p.Asp458Val)

HGVS:

NC_000004.12:g.54725883A>T
NG_007456.1:g.72889A>T
NM_000222.3:c.1373A>TMANE SELECT
NM_001093772.2:c.1373A>T
NM_001385284.1:c.1376A>T
NM_001385285.1:c.1373A>T
NM_001385286.1:c.1373A>T
NM_001385288.1:c.1376A>T
NM_001385290.1:c.1376A>T
NM_001385292.1:c.1376A>T
NP_000213.1:p.Asp458Val
NP_000213.1:p.Asp458Val
NP_001087241.1:p.Asp458Val
NP_001372213.1:p.Asp459Val
NP_001372214.1:p.Asp458Val
NP_001372215.1:p.Asp458Val
NP_001372217.1:p.Asp459Val
NP_001372219.1:p.Asp459Val
NP_001372221.1:p.Asp459Val
LRG_307t1:c.1373A>T
LRG_307:g.72889A>T
LRG_307p1:p.Asp458Val
NC_000004.11:g.55592049A>T
NM_000222.2:c.1373A>T

Protein change:

D458V

Links:

dbSNP: rs1553891403

NCBI 1000 Genomes Browser:

rs1553891403

Molecular consequence:

NM_000222.3:c.1373A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1373A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1376A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1373A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1373A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1376A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1376A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1376A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000755109	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005059864	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 25, 2023)	unknown	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

SCV000755109

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 26, 2022)

germline

clinical testing

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

SCV005059864

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 25, 2023)

unknown

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
not provided	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000755109.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 528614). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 458 of the KIT protein (p.Asp458Val).

#	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

From Baylor Genetics, SCV005059864.1

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

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

Last Updated: Sep 29, 2024

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