NM_000222.3(KIT):c.792C>A (p.His264Gln) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 19, 2021
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:: RCV001244299.10

Allele description [Variation Report for NM_000222.3(KIT):c.792C>A (p.His264Gln)]

NM_000222.3(KIT):c.792C>A (p.His264Gln)

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.792C>A (p.His264Gln)

HGVS:

NC_000004.12:g.54703759C>A
NG_007456.1:g.50765C>A
NM_000222.3:c.792C>AMANE SELECT
NM_001093772.2:c.792C>A
NM_001385284.1:c.795C>A
NM_001385285.1:c.792C>A
NM_001385286.1:c.792C>A
NM_001385288.1:c.795C>A
NM_001385290.1:c.795C>A
NM_001385292.1:c.795C>A
NP_000213.1:p.His264Gln
NP_001087241.1:p.His264Gln
NP_001372213.1:p.His265Gln
NP_001372214.1:p.His264Gln
NP_001372215.1:p.His264Gln
NP_001372217.1:p.His265Gln
NP_001372219.1:p.His265Gln
NP_001372221.1:p.His265Gln
LRG_307t1:c.792C>A
LRG_307:g.50765C>A
NC_000004.11:g.55569925C>A
NM_000222.2:c.792C>A

Protein change:

H264Q

Links:

dbSNP: rs753102574

NCBI 1000 Genomes Browser:

rs753102574

Molecular consequence:

NM_000222.3:c.792C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.792C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.795C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.792C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.792C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.795C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.795C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.795C>A - 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
SCV001417508	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 19, 2021)	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

SCV001417508

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 19, 2021)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001417508.6

#	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 histidine with glutamine at codon 264 of the KIT protein (p.His264Gln). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and glutamine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KIT-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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: Apr 15, 2024

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