Submissions for variant NM_007294.4(BRCA1):c.1612_1616del (p.Gln538fs)

dbSNP: rs587776480

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)	RCV000144201	SCV000299627	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	RCV000561524	SCV000665375	pathogenic	Hereditary cancer-predisposing syndrome	2017-06-23	criteria provided, single submitter	clinical testing	The c.1612_1616delCAAAC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 5 nucleotides at nucleotide positions 1612 to 1616, causing a translational frameshift with a predicted alternate stop codon (p.Q538Gfs*11). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496736	SCV001589725	pathogenic	Hereditary breast ovarian cancer syndrome	2020-01-30	criteria provided, single submitter	clinical testing	Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 156184). This sequence change creates a premature translational stop signal (p.Gln538Glyfs*11) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency).
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005365042	SCV005914248	pathogenic	Fanconi anemia, complementation group S	2024-05-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000561524	SCV006063580	pathogenic	Hereditary cancer-predisposing syndrome	2024-02-20	criteria provided, single submitter	clinical testing	This variant deletes 5 nucleotides 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 reported in at least two individuals affected with ovarian cancer (PMID: 30040829, 32772980). 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.
Sharing Clinical Reports Project (SCRP)	RCV000144201	SCV000189274	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-14	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496736	SCV000587150	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research