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NM_000222.3(KIT):c.1351T>C (p.Ser451Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Apr 9, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV001011082.7

Allele description [Variation Report for NM_000222.3(KIT):c.1351T>C (p.Ser451Pro)]

NM_000222.3(KIT):c.1351T>C (p.Ser451Pro)

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.1351T>C (p.Ser451Pro)
HGVS:
  • NC_000004.12:g.54725861T>C
  • NG_007456.1:g.72867T>C
  • NM_000222.3:c.1351T>CMANE SELECT
  • NM_001093772.2:c.1351T>C
  • NM_001385284.1:c.1354T>C
  • NM_001385285.1:c.1351T>C
  • NM_001385286.1:c.1351T>C
  • NM_001385288.1:c.1354T>C
  • NM_001385290.1:c.1354T>C
  • NM_001385292.1:c.1354T>C
  • NP_000213.1:p.Ser451Pro
  • NP_000213.1:p.Ser451Pro
  • NP_001087241.1:p.Ser451Pro
  • NP_001372213.1:p.Ser452Pro
  • NP_001372214.1:p.Ser451Pro
  • NP_001372215.1:p.Ser451Pro
  • NP_001372217.1:p.Ser452Pro
  • NP_001372219.1:p.Ser452Pro
  • NP_001372221.1:p.Ser452Pro
  • LRG_307t1:c.1351T>C
  • LRG_307:g.72867T>C
  • LRG_307p1:p.Ser451Pro
  • NC_000004.11:g.55592027T>C
  • NM_000222.2:c.1351T>C
Protein change:
S451P
Links:
dbSNP: rs145183977
NCBI 1000 Genomes Browser:
rs145183977
Molecular consequence:
  • NM_000222.3:c.1351T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001093772.2:c.1351T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385284.1:c.1354T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385285.1:c.1351T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385286.1:c.1351T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385288.1:c.1354T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385290.1:c.1354T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385292.1:c.1354T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001171363Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely benign
(Apr 9, 2024) 		germlineclinical testing

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

Citation Link,

SCV002536385Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)		Uncertain significance
(Mar 18, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

Pritchard AL, Johansson PA, Nathan V, Howlie M, Symmons J, Palmer JM, Hayward NK.

PLoS One. 2018;13(4):e0194098. doi: 10.1371/journal.pone.0194098.

PubMed [citation]
PMID:
29641532
PMCID:
PMC5894988

Details of each submission

From Ambry Genetics, SCV001171363.5

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

From Sema4, Sema4, SCV002536385.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024