Submissions for variant NM_007294.4(BRCA1):c.2702T>C (p.Phe901Ser)

dbSNP: rs397507202

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000221978	SCV000274785	likely benign	Hereditary cancer-predisposing syndrome	2020-09-29	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.
Counsyl	RCV000031063	SCV000488946	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2016-07-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000221978	SCV000909335	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-06	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with serine at codon 901 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large breast cancer case-control study, this variant has been observed in 2/60466 cases and 1/53461 controls (PMID: 33471991). This variant has been identified in 1/250872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513280	SCV003015419	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 901 of the BRCA1 protein (p.Phe901Ser). This variant is present in population databases (rs397507202, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 37482). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000221978	SCV003849415	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).
Sharing Clinical Reports Project (SCRP)	RCV000031063	SCV000053659	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2011-06-21	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001689580	SCV001906389	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001689580	SCV001952873	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001689580	SCV001963244	likely benign	not provided		no assertion criteria provided	clinical testing