Submissions for variant NM_007294.4(BRCA1):c.932C>T (p.Pro311Leu)

dbSNP: rs1301795658

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000773301	SCV000906993	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-22	criteria provided, single submitter	clinical testing	This missense variant replaces proline with leucine at codon 311 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. A multifactorial analysis has reported likelihood ratios for pathogenicity of 1.0673 and 0.1437 based on co-occurrence and family history, respectively (PMID: 31131967). This variant has been identified in 1/251380 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	RCV000810336	SCV000950531	likely benign	Hereditary breast ovarian cancer syndrome	2023-10-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985452	SCV001133658	uncertain significance	not provided	2021-02-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000773301	SCV002686745	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-05	criteria provided, single submitter	clinical testing	The p.P311L variant (also known as c.932C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 932. The proline at codon 311 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000773301	SCV003846279	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).
All of Us Research Program, National Institutes of Health	RCV004000000	SCV004818393	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2023-03-23	criteria provided, single submitter	clinical testing	This missense variant replaces proline with leucine at codon 311 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. A multifactorial analysis has reported likelihood ratios for pathogenicity of 1.0673 and 0.1437 based on co-occurrence and family history, respectively (PMID: 31131967). This variant has been identified in 1/251380 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.