Submissions for variant NM_007294.4(BRCA1):c.4386dup (p.Tyr1463fs)

dbSNP: rs786204267

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)	RCV000168509	SCV000300111	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508646	SCV000605875	pathogenic	not provided	2016-08-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000257898	SCV000699140	likely pathogenic	Hereditary breast ovarian cancer syndrome	2017-02-20	criteria provided, single submitter	clinical testing	Variant summary: The BRCA1 c.4386dupA (p.Tyr1463Ilefs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.4391delC [p.Pro1464fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in the large control population database ExAC (0/121374 control chromosomes). Another similar variant BRCA1 Tyr1463* is a known pathogenic. In addition, multiple clinical diagnostic laboratories/databases have classified this variant as pathogenic or likely pathogenic. Taken together, this variant is classified as likely pathogenic.
Ambry Genetics	RCV002326926	SCV002629078	pathogenic	Hereditary cancer-predisposing syndrome	2017-08-11	criteria provided, single submitter	clinical testing	The c.4386dupA pathogenic mutation, located in coding exon 12 of the BRCA1 gene, results from a duplication of A at nucleotide position 4386, causing a translational frameshift with a predicted alternate stop codon (p.Y1463Ifs*13). 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.
Baylor Genetics	RCV000168509	SCV004216929	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-10	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003491924	SCV004240266	pathogenic	Breast and/or ovarian cancer	2023-06-02	criteria provided, single submitter	clinical testing