U.S. flag

An official website of the United States government

NM_000222.3(KIT):c.1964A>G (p.Asn655Ser) AND Gastrointestinal stromal tumor

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 23, 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:
RCV000701684.10

Allele description [Variation Report for NM_000222.3(KIT):c.1964A>G (p.Asn655Ser)]

NM_000222.3(KIT):c.1964A>G (p.Asn655Ser)

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.1964A>G (p.Asn655Ser)
HGVS:
  • NC_000004.12:g.54728095A>G
  • NG_007456.1:g.75101A>G
  • NM_000222.3:c.1964A>GMANE SELECT
  • NM_001093772.2:c.1952A>G
  • NM_001385284.1:c.1967A>G
  • NM_001385285.1:c.1964A>G
  • NM_001385286.1:c.1952A>G
  • NM_001385288.1:c.1955A>G
  • NM_001385290.1:c.1967A>G
  • NM_001385292.1:c.1955A>G
  • NP_000213.1:p.Asn655Ser
  • NP_000213.1:p.Asn655Ser
  • NP_001087241.1:p.Asn651Ser
  • NP_001372213.1:p.Asn656Ser
  • NP_001372214.1:p.Asn655Ser
  • NP_001372215.1:p.Asn651Ser
  • NP_001372217.1:p.Asn652Ser
  • NP_001372219.1:p.Asn656Ser
  • NP_001372221.1:p.Asn652Ser
  • LRG_307t1:c.1964A>G
  • LRG_307:g.75101A>G
  • LRG_307p1:p.Asn655Ser
  • NC_000004.11:g.55594261A>G
  • NM_000222.2:c.1964A>G
Protein change:
N651S
Links:
dbSNP: rs1057519707
NCBI 1000 Genomes Browser:
rs1057519707
Molecular consequence:
  • NM_000222.3:c.1964A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001093772.2:c.1952A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385284.1:c.1967A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385285.1:c.1964A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385286.1:c.1952A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385288.1:c.1955A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385290.1:c.1967A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385292.1:c.1955A>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000830496Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 23, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Characterization of tyrosine kinase I domain c-kit gene mutation Asn655Lys newly found in primary jejunal gastrointestinal stromal tumor.

Kinoshita K, Hirota S, Isozaki K, Nishitani A, Tsutsui S, Watabe K, Tamura S, Ishikawa T, Kanda T, Nishida T, Hayashi N.

Am J Gastroenterol. 2007 May;102(5):1134-6. No abstract available.

PubMed [citation]
PMID:
17489795

Spectrum of mutations in gastrointestinal stromal tumor patients - a population-based study from Slovakia.

Minárik G, Plank L, Lasabová Z, Szemes T, Burjanivová T, Szépe P, Buzalková V, Porubský D, Sufliarsky J.

APMIS. 2013 Jun;121(6):539-48. doi: 10.1111/apm.12019. Epub 2012 Oct 27.

PubMed [citation]
PMID:
23106360
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000830496.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 655 of the KIT protein (p.Asn655Ser). 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: 375922). 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 disruptive. This variant disrupts the p.Asn655 amino acid residue in KIT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17489795, 23106360, 33212994; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024