NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: May 2, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000166450.6

Allele description [Variation Report for NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)]

NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)
HGVS:
  • NC_000017.11:g.43094148A>T
  • NG_005905.2:g.123836T>A
  • NM_007294.3:c.1383T>A
  • NM_007294.4:c.1383T>AMANE SELECT
  • NM_007297.4:c.1242T>A
  • NM_007298.3:c.787+596T>A
  • NM_007299.4:c.787+596T>A
  • NM_007300.4:c.1383T>A
  • NP_009225.1:p.Phe461Leu
  • NP_009225.1:p.Phe461Leu
  • NP_009228.2:p.Phe414Leu
  • NP_009231.2:p.Phe461Leu
  • LRG_292t1:c.1383T>A
  • LRG_292:g.123836T>A
  • LRG_292p1:p.Phe461Leu
  • NC_000017.10:g.41246165A>T
  • NM_007294.4:c.1383T>A
  • NR_027676.2:n.1560T>A
  • P38398:p.Phe461Leu
  • U14680.1:n.1502T>A
  • p.F461L
Protein change:
F414L
Links:
UniProtKB: P38398#VAR_007765; dbSNP: rs56046357
NCBI 1000 Genomes Browser:
rs56046357
Molecular consequence:
  • NM_007298.3:c.787+596T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+596T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.1242T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.1560T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000217246Ambry Geneticscriteria provided, single submitter
Uncertain significance
(May 2, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV000909384Color Health, Inccriteria provided, single submitter
Uncertain significance
(Apr 9, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Understanding missense mutations in the BRCA1 gene: an evolutionary approach.

Fleming MA, Potter JD, Ramirez CJ, Ostrander GK, Ostrander EA.

Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1151-6. Epub 2003 Jan 16.

PubMed [citation]
PMID:
12531920
PMCID:
PMC298742

Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.

Abkevich V, Zharkikh A, Deffenbaugh AM, Frank D, Chen Y, Shattuck D, Skolnick MH, Gutin A, Tavtigian SV.

J Med Genet. 2004 Jul;41(7):492-507.

PubMed [citation]
PMID:
15235020
PMCID:
PMC1735826
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000217246.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (6)

Description

The p.F461L variant (also known as c.1383T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 1383. The phenylalanine at codon 461 is replaced by leucine, an amino acid with highly similar properties. This alteration has been classified as a variant of uncertain significance based on a classification system using interspecific sequence variation and has also been reported in an exome cohort (Abkevich V et al. J. Med. Genet., 2004 Jul;41:492-507; Amendola LM et al. Genome Res., 2015 Mar;25:305-15). This alteration has also been identified in one early-onset familial breast cancer kindred (<span style="background-color:initial">Katagiri T, J. Hum. Genet. 1998 ; 43(1):42-8).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000909384.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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