Submissions for variant NM_007294.4(BRCA1):c.784C>T (p.Gln262Ter)

dbSNP: rs886037979

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)	RCV000240999	SCV000299483	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000240999	SCV000326408	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001026872	SCV001189342	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-15	criteria provided, single submitter	clinical testing	The p.Q262* pathogenic mutation (also known as c.784C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 784. This changes the amino acid from a glutamine to a stop codon within coding exon 9. 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	RCV001207336	SCV001378681	pathogenic	Hereditary breast ovarian cancer syndrome	2021-12-05	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: 254380). This premature translational stop signal has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 27553291, 28176296, 29446198, 30702160). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln262*) 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).
Color Diagnostics, LLC DBA Color Health	RCV001026872	SCV004361095	pathogenic	Hereditary cancer-predisposing syndrome	2023-07-06	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 27553291, 28176296, 34721658). 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000240999	SCV000733665	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727656	SCV001970755	pathogenic	not provided		no assertion criteria provided	clinical testing