Submissions for variant NM_007294.4(BRCA1):c.976G>C (p.Glu326Gln)

gnomAD frequency: 0.00004  dbSNP: rs773433679

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985453	SCV001133660	uncertain significance	not provided	2019-01-04	criteria provided, single submitter	clinical testing
Invitae	RCV001052638	SCV001216859	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001824909	SCV002074372	uncertain significance	not specified	2022-01-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000985453	SCV002102653	uncertain significance	not provided	2022-02-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1095G>C
Ambry Genetics	RCV002382218	SCV002693953	likely benign	Hereditary cancer-predisposing syndrome	2023-10-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
University of Washington Department of Laboratory Medicine, University of Washington	RCV002382218	SCV003846254	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000985453	SCV002034319	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000985453	SCV002035790	likely benign	not provided		no assertion criteria provided	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003229606	SCV003927209	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-05	no assertion criteria provided	clinical testing	BRCA1 (p.Glu326Gln): This sequence change replaces glutamic acid with glutamine at codon 326 of the BRCA1 protein (p.Glu326Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant has not been reported in the literature in individuals with BRCA1-related disease. In-silico predictions show pathogenic computational verdict based on 10 pathogenic predictions from BayesDel_addAF, DANN, DEOGEN2, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster and SIFT vs 2 benign predictions from EIGEN and PrimateAI. Therefore, it has been classified as a Variant of Uncertain Significance.