Submissions for variant NM_007294.4(BRCA1):c.1630C>T (p.Gln544Ter)

dbSNP: rs80356952

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111656	SCV000299629	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	RCV000111656	SCV000296326	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-04-16	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111656	SCV000325113	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000581056	SCV000682974	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-27	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. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in individuals affected with breast and ovarian cancer (PMID: 21913181; BIC accession number 4088; Color internal data). 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.
Ambry Genetics	RCV000581056	SCV001172957	pathogenic	Hereditary cancer-predisposing syndrome	2019-07-02	criteria provided, single submitter	clinical testing	The p.Q544* pathogenic mutation (also known as c.1630C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1630. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration was seen in an ovarian cancer patient who also had a mutation in RAD51D (Eoh KJ et al. Cancer Res Treat, 2018 Jul;50:917-925). 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.
Invitae	RCV000496741	SCV001590813	pathogenic	Hereditary breast ovarian cancer syndrome	2021-09-16	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: 54313). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 21913181, 22762150, 29020732, 29446198). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln544*) 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).
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111656	SCV000144146	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-22	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496741	SCV000587153	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research