Submissions for variant NM_007294.4(BRCA1):c.1287dup (p.Asp430fs)

dbSNP: rs80357576

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111582	SCV000282257	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-22	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneDx	RCV000235124	SCV000210010	pathogenic	not provided	2023-06-20	criteria provided, single submitter	clinical testing	Frameshift 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 1406dupA; This variant is associated with the following publications: (PMID: 26187060, 31492746, 28888541, 22160602, 16683254, 9150151, 14574155, 16528604, 29176636, 29446198, 10952774, 20104584)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111582	SCV000325004	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570848	SCV000660978	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-28	criteria provided, single submitter	clinical testing	The c.1287dupA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of A at nucleotide position 1287, causing a translational frameshift with a predicted alternate stop codon (p.D430Rfs*6). This mutation has previously been reported in multiple individuals and families affected with breast and/or ovarian cancer, and, specifically, has been reported as a recurrent mutation in the Dutch population (Peelen T et al. Am. J. Hum. Genet. 1997 May;60:1041-9; Schneegans SM et al. Fam. Cancer. 2012 Jun;11:181-8; Sinilnikova OM et al. Fam. Cancer. 2006;5:15-20; Piek JM et al. Fam. Cancer. 2003;2:73-8). This mutation has also been designated as 1406insA in the published literature. In addition to the clinical data presented in the literature, 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.
Color Diagnostics, LLC DBA Color Health	RCV000570848	SCV000911643	pathogenic	Hereditary cancer-predisposing syndrome	2023-04-19	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in one individual each affected with breast cancer (PMID: 24249303) and intraperitoneal cancer (PMID: 14574155) and in suspected hereditary breast and ovarian cancer families (PMID: 9150151, 16528604, 16683254, 31745186). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496353	SCV001591290	pathogenic	Hereditary breast ovarian cancer syndrome	2023-10-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asp430Argfs*6) 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: 9150151, 14574155, 16528604, 16683254, 22160602). This variant is also known as 1406insA. ClinVar contains an entry for this variant (Variation ID: 54186). For these reasons, this variant has been classified as Pathogenic.
All of Us Research Program, National Institutes of Health	RCV000111582	SCV004818346	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-06-08	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in one individual each affected with breast cancer (PMID: 24249303) and intraperitoneal cancer (PMID: 14574155) and in suspected hereditary breast and ovarian cancer families (PMID: 9150151, 16528604, 16683254, 31745186). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111582	SCV000144050	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-07-10	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000111582	SCV000297584	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-03-09	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496353	SCV000587117	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000235124	SCV001741327	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000235124	SCV001906166	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000235124	SCV001931778	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000235124	SCV001976009	pathogenic	not provided		no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000111582	SCV004171650	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-11-24	no assertion criteria provided	clinical testing