Submissions for variant NM_007294.4(BRCA1):c.139dup (p.Cys47fs)

dbSNP: rs80357734

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111869	SCV000299411	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.
Ambry Genetics	RCV001011387	SCV001171699	pathogenic	Hereditary cancer-predisposing syndrome	2018-07-02	criteria provided, single submitter	clinical testing	The c.139dupT pathogenic mutation, located in coding exon 3 of the BRCA1 gene, results from a duplication of T at nucleotide position 139, causing a translational frameshift with a predicted alternate stop codon (p.C47Lfs*19). 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.
Invitae	RCV000496948	SCV002189550	pathogenic	Hereditary breast ovarian cancer syndrome	2022-07-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 125570). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys47Leufs*19) 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).
Baylor Genetics	RCV000111869	SCV004216927	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477484	SCV004222562	pathogenic	not provided	2022-12-23	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. The variant has not been reported in individuals with BRCA1-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). However, it has been reported in an individual with breast and/or ovarian cancer (BIC (https://research.nhgri.nih.gov/projects/bic)). Based on the available information, this variant is classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111869	SCV000144446	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-04-06	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496948	SCV000587019	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research