Submissions for variant NM_007294.4(BRCA1):c.3706_3713del (p.Asn1236fs)

dbSNP: rs80357552

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)	RCV000112158	SCV000299999	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	RCV000509675	SCV000607972	pathogenic	Hereditary cancer-predisposing syndrome	2022-04-22	criteria provided, single submitter	clinical testing	The c.3706_3713delAATATACC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 8 nucleotides at nucleotide positions 3706 to 3713, causing a translational frameshift with a predicted alternate stop codon (p.N1236Ffs*5). This alteration has been reported in one individual diagnosed with breast cancer before the age of 45 (Haffty BG et al. Ann. Oncol. 2009 Oct;20(10):1653-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
GeneDx	RCV000657206	SCV000778932	pathogenic	not provided	2024-11-12	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 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 3825_3832del; 3825del8; This variant is associated with the following publications: (PMID: 38538877, 19491284, 31853058)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000657206	SCV000887676	pathogenic	not provided	2018-01-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496875	SCV001586298	pathogenic	Hereditary breast ovarian cancer syndrome	2024-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn1236Phefs*5) 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 early onset breast cancer (PMID: 19491284). This variant is also known as 3825del8. ClinVar contains an entry for this variant (Variation ID: 54969). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112158	SCV000144841	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496875	SCV000587334	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research