NM_000222.3(KIT):c.1780A>C (p.Thr594Pro) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 28, 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:: RCV001970981.7

Allele description [Variation Report for NM_000222.3(KIT):c.1780A>C (p.Thr594Pro)]

NM_000222.3(KIT):c.1780A>C (p.Thr594Pro)

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.1780A>C (p.Thr594Pro)

HGVS:

NC_000004.12:g.54727828A>C
NG_007456.1:g.74834A>C
NM_000222.3:c.1780A>CMANE SELECT
NM_001093772.2:c.1768A>C
NM_001385284.1:c.1783A>C
NM_001385285.1:c.1780A>C
NM_001385286.1:c.1768A>C
NM_001385288.1:c.1771A>C
NM_001385290.1:c.1783A>C
NM_001385292.1:c.1771A>C
NP_000213.1:p.Thr594Pro
NP_001087241.1:p.Thr590Pro
NP_001372213.1:p.Thr595Pro
NP_001372214.1:p.Thr594Pro
NP_001372215.1:p.Thr590Pro
NP_001372217.1:p.Thr591Pro
NP_001372219.1:p.Thr595Pro
NP_001372221.1:p.Thr591Pro
LRG_307:g.74834A>C
NC_000004.11:g.55593994A>C

Protein change:

T590P

Links:

dbSNP: rs2109779265

NCBI 1000 Genomes Browser:

rs2109779265

Molecular consequence:

NM_000222.3:c.1780A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.1768A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.1783A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.1780A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.1768A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.1771A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.1783A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.1771A>C - 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
SCV002265371	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 28, 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

SCV002265371

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 28, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002265371.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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). This sequence change replaces threonine with proline at codon 594 of the KIT protein (p.Thr594Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline.

#	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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