NM_000222.3(KIT):c.52C>T (p.Leu18Phe) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 15, 2024
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:: RCV000470178.20

Allele description [Variation Report for NM_000222.3(KIT):c.52C>T (p.Leu18Phe)]

NM_000222.3(KIT):c.52C>T (p.Leu18Phe)

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.52C>T (p.Leu18Phe)

HGVS:

NC_000004.12:g.54658066C>T
NG_007456.1:g.5073C>T
NM_000222.3:c.52C>TMANE SELECT
NM_001093772.2:c.52C>T
NM_001385284.1:c.52C>T
NM_001385285.1:c.52C>T
NM_001385286.1:c.52C>T
NM_001385288.1:c.52C>T
NM_001385290.1:c.52C>T
NM_001385292.1:c.52C>T
NP_000213.1:p.Leu18Phe
NP_000213.1:p.Leu18Phe
NP_001087241.1:p.Leu18Phe
NP_001372213.1:p.Leu18Phe
NP_001372214.1:p.Leu18Phe
NP_001372215.1:p.Leu18Phe
NP_001372217.1:p.Leu18Phe
NP_001372219.1:p.Leu18Phe
NP_001372221.1:p.Leu18Phe
LRG_307t1:c.52C>T
LRG_307:g.5073C>T
LRG_307p1:p.Leu18Phe
NC_000004.11:g.55524233C>T
NM_000222.2:c.52C>T

Protein change:

L18F

Links:

dbSNP: rs370787811

NCBI 1000 Genomes Browser:

rs370787811

Molecular consequence:

NM_000222.3:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001093772.2:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385284.1:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385285.1:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385286.1:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385288.1:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385290.1:c.52C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385292.1:c.52C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550099	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004198080	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 15, 2024)	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

SCV000550099

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

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

SCV004198080

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 15, 2024)

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000550099.10

#	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 leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 18 of the KIT protein (p.Leu18Phe). This variant is present in population databases (rs370787811, gnomAD 0.009%). 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: 409759). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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, SCV004198080.2

#	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: Nov 24, 2024

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