Submissions for variant NM_007294.4(BRCA1):c.1863T>C (p.His621=)

dbSNP: rs786201460

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)	RCV000495006	SCV000578083	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics	RCV000163689	SCV000214263	likely benign	Hereditary cancer-predisposing syndrome	2017-09-06	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.
GeneDx	RCV000438389	SCV000525814	likely benign	not specified	2016-03-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001407806	SCV001609788	likely benign	Hereditary breast ovarian cancer syndrome	2023-12-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003407608	SCV004140631	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	BRCA1: PM2:Supporting, BP4, BP7
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353440	SCV000591353	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.His621His variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It was not identified in the literature, nor the UMD, LOVD or BIC databases. The prevalence of this variant in the general population is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for it. This variant meets our laboratory's classification criteria as predicted benign.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735486	SCV000863623	likely benign	Breast and/or ovarian cancer	2012-12-13	no assertion criteria provided	clinical testing