ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.817C>T (p.Pro273Ser)

dbSNP: rs1597879824
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985450 SCV001133652 uncertain significance not provided 2018-11-16 criteria provided, single submitter clinical testing
Invitae RCV001858620 SCV002234118 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 273 of the BRCA1 protein (p.Pro273Ser). This variant is not present in population databases (gnomAD no frequency). 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: 801088). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV002427437 SCV002680070 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-24 criteria provided, single submitter clinical testing The p.P273S variant (also known as c.817C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 817. The proline at codon 273 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 RCV002427437 SCV003847916 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).
Color Diagnostics, LLC DBA Color Health RCV002427437 SCV004361093 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 273 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000985450 SCV004565067 uncertain significance not provided 2023-03-28 criteria provided, single submitter clinical testing The BRCA1 c.817C>T; p.Pro273Ser variant (rs1597879824), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 801088). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.593). Due to limited information, the clinical significance of this variant is uncertain at this time.

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