NM_000222.3(KIT):c.1895C>T (p.Thr632Ile) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 23, 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:: RCV000556564.10

Allele description [Variation Report for NM_000222.3(KIT):c.1895C>T (p.Thr632Ile)]

NM_000222.3(KIT):c.1895C>T (p.Thr632Ile)

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.1895C>T (p.Thr632Ile)

HGVS:

NC_000004.12:g.54728026C>T
NG_007456.1:g.75032C>T
NM_000222.3:c.1895C>TMANE SELECT
NM_001093772.2:c.1883C>T
NM_001385284.1:c.1898C>T
NM_001385285.1:c.1895C>T
NM_001385286.1:c.1883C>T
NM_001385288.1:c.1886C>T
NM_001385290.1:c.1898C>T
NM_001385292.1:c.1886C>T
NP_000213.1:p.Thr632Ile
NP_000213.1:p.Thr632Ile
NP_001087241.1:p.Thr628Ile
NP_001372213.1:p.Thr633Ile
NP_001372214.1:p.Thr632Ile
NP_001372215.1:p.Thr628Ile
NP_001372217.1:p.Thr629Ile
NP_001372219.1:p.Thr633Ile
NP_001372221.1:p.Thr629Ile
LRG_307t1:c.1895C>T
LRG_307:g.75032C>T
LRG_307p1:p.Thr632Ile
NC_000004.11:g.55594192C>T
NM_000222.2:c.1895C>T

Protein change:

T628I

Links:

dbSNP: rs1553891944

NCBI 1000 Genomes Browser:

rs1553891944

Molecular consequence:

NM_000222.3:c.1895C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1883C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1898C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1895C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1883C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1886C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1898C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1886C>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630447	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004190407	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 12, 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

SCV000630447

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 23, 2023)

germline

clinical testing

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

SCV004190407

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 12, 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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 Invitae, SCV000630447.6

#	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 threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 632 of the KIT protein (p.Thr632Ile). 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: 458897). 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. 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

From Baylor Genetics, SCV004190407.1

#	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: Jul 15, 2024

ClinVar

Relating variation to medicine