NM_000222.3(KIT):c.1453C>G (p.His485Asp) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 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:: RCV003639728.3

Allele description [Variation Report for NM_000222.3(KIT):c.1453C>G (p.His485Asp)]

NM_000222.3(KIT):c.1453C>G (p.His485Asp)

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.1453C>G (p.His485Asp)

HGVS:

NC_000004.12:g.54725963C>G
NG_007456.1:g.72969C>G
NM_000222.3:c.1453C>GMANE SELECT
NM_001093772.2:c.1453C>G
NM_001385284.1:c.1456C>G
NM_001385285.1:c.1453C>G
NM_001385286.1:c.1453C>G
NM_001385288.1:c.1456C>G
NM_001385290.1:c.1456C>G
NM_001385292.1:c.1456C>G
NP_000213.1:p.His485Asp
NP_000213.1:p.His485Asp
NP_001087241.1:p.His485Asp
NP_001372213.1:p.His486Asp
NP_001372214.1:p.His485Asp
NP_001372215.1:p.His485Asp
NP_001372217.1:p.His486Asp
NP_001372219.1:p.His486Asp
NP_001372221.1:p.His486Asp
LRG_307t1:c.1453C>G
LRG_307:g.72969C>G
LRG_307p1:p.His485Asp
NC_000004.11:g.55592129C>G
NM_000222.2:c.1453C>G

Protein change:

H485D

Molecular consequence:

NM_000222.3:c.1453C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1453C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1456C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1453C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1453C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1456C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1456C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1456C>G - 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
SCV004408343	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 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

SCV004408343

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 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, SCV004408343.1

#	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 affected with KIT-related conditions. 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. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 485 of the KIT protein (p.His485Asp).

#	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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