Submissions for variant NM_007294.4(BRCA1):c.4834C>T (p.Gln1612Ter)

dbSNP: rs786202064

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)	RCV000241386	SCV000300166	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	RCV000164690	SCV000215357	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-28	criteria provided, single submitter	clinical testing	The p.Q1612* pathogenic mutation (also known as c.4834C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4834. This changes the amino acid from a glutamine to a stop codon within coding exon 14. 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000241386	SCV000326047	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164690	SCV000683219	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-01	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 15 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 an individual with personal and/or family history of BRCA1-associated cancers (PMID: 31954625). 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	RCV000496345	SCV002226066	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-08	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: 185295). This variant is also known as 4897C>T. This premature translational stop signal has been observed in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 29446198, 29470806, 30555256, 31954625). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1612*) 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).
Baylor Genetics	RCV000241386	SCV004212758	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-09-22	criteria provided, single submitter	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496345	SCV000587429	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research