Submissions for variant NM_007294.4(BRCA1):c.5100A>G (p.Thr1700=) (rs45519437)

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)	RCV000494789	SCV000578340	likely benign	Breast-ovarian cancer, familial 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	RCV000163399	SCV000213940	likely benign	Hereditary cancer-predisposing syndrome	2014-12-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV001085698	SCV000253509	likely benign	Hereditary breast and ovarian cancer syndrome	2020-11-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000428938	SCV000512314	benign	not specified	2015-04-27	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.
Color Health, Inc	RCV000163399	SCV000683253	likely benign	Hereditary cancer-predisposing syndrome	2015-12-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758840	SCV000887712	likely benign	not provided	2017-08-30	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV001353890	SCV000591579	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Thr1700Thr 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 has not been previously identified by our laboratory, but has been reported in the literature in a study involving 55,630 probands (frequency was not provided) from families with familiar breast and ovarian cancers, and classified as a variant of benign significance. In addition, no control chromosomes were tested to establish the frequency of the variant in the general population (Judkins 2005). This variant is listed in the dbSNP database (ID#:rs45519437) but no frequency information was provided, and so the prevalence of this variant in the population is not known. The variant was also identified in the UMD database (2x) and once in the presence of a second unclassified variant, although this does not provide any additional clarification as to the clinical significance of this variant. In summary, based on the above information, this variant is predicted benign.
Brotman Baty Institute,University of Washington	RCV000494789	SCV001237599	not provided	Breast-ovarian cancer, familial 1		no assertion provided	in vitro