Submissions for variant NM_007294.4(BRCA1):c.403A>T (p.Lys135Ter)

dbSNP: rs879255485

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000239031	SCV000783514	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Baylor Genetics	RCV000239031	SCV004215152	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-04-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496796	SCV004314293	pathogenic	Hereditary breast ovarian cancer syndrome	2023-11-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys135*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 252876). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV004609332	SCV005100591	pathogenic	Hereditary cancer-predisposing syndrome	2024-05-31	criteria provided, single submitter	clinical testing	The p.K135* pathogenic mutation (also known as c.403A>T), located in coding exon 5 of the BRCA1 gene, results from an A to T substitution at nucleotide position 403. This changes the amino acid from a lysine to a stop codon within coding exon 5. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Sharing Clinical Reports Project (SCRP)	RCV000239031	SCV000297479	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2010-05-10	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496796	SCV000587050	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research