Submissions for variant NM_007294.4(BRCA1):c.737del (p.Asp245_Leu246insTer)

dbSNP: rs397509312

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000241020	SCV000299477	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000497268	SCV000210003	pathogenic	not provided	2024-09-17	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 856del and (p.Asp245_Leu246isTer); This variant is associated with the following publications: (PMID: 31159747, 20104584, 21324516, 36980780, 31409081, 29785153, 37239058)
GeneKor MSA	RCV000049114	SCV000296787	pathogenic	Familial cancer of breast	2020-01-01	criteria provided, single submitter	clinical testing	This variation is a deletion of 1 nucleotide from exon 11 of the BRCA1 mRNA (c.737delT), causing a frameshift at codon 246. This creates a premature translation stop signal at this position and is expected to result in an absent or disrupted protein product. This mutation has been described in the mutation database ClinVar (Variation ID: 55683).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496359	SCV001589895	pathogenic	Hereditary breast ovarian cancer syndrome	2024-03-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu246*) 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 premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 21324516, 29785153). This variant is also known as c.856delT. ClinVar contains an entry for this variant (Variation ID: 55683). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496359	SCV000587074	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research