NM_000222.3(KIT):c.1455C>A (p.His485Gln) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 23, 2022
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:: RCV001369882.8

Allele description [Variation Report for NM_000222.3(KIT):c.1455C>A (p.His485Gln)]

NM_000222.3(KIT):c.1455C>A (p.His485Gln)

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.1455C>A (p.His485Gln)

HGVS:

NC_000004.12:g.54725965C>A
NG_007456.1:g.72971C>A
NM_000222.3:c.1455C>AMANE SELECT
NM_001093772.2:c.1455C>A
NM_001385284.1:c.1458C>A
NM_001385285.1:c.1455C>A
NM_001385286.1:c.1455C>A
NM_001385288.1:c.1458C>A
NM_001385290.1:c.1458C>A
NM_001385292.1:c.1458C>A
NP_000213.1:p.His485Gln
NP_001087241.1:p.His485Gln
NP_001372213.1:p.His486Gln
NP_001372214.1:p.His485Gln
NP_001372215.1:p.His485Gln
NP_001372217.1:p.His486Gln
NP_001372219.1:p.His486Gln
NP_001372221.1:p.His486Gln
LRG_307:g.72971C>A
NC_000004.11:g.55592131C>A

Protein change:

H485Q

Links:

dbSNP: rs1331885453

NCBI 1000 Genomes Browser:

rs1331885453

Molecular consequence:

NM_000222.3:c.1455C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1455C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1458C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1455C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1455C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1458C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1458C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1458C>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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Homo sapiens translocase of inner mitochondrial membrane 29 (TIMM29), mRNA
Homo sapiens translocase of inner mitochondrial membrane 29 (TIMM29), mRNA
gi|34328079|ref|NM_138358.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001566336	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 23, 2022)	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

SCV001566336

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 23, 2022)

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, SCV001566336.4

#	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, which is basic and polar, with glutamine, which is neutral and polar, at codon 485 of the KIT protein (p.His485Gln). This variant is not present in population databases (gnomAD no frequency). 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: 1060447). 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 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: Sep 29, 2024

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