ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1721T>C (p.Leu574Pro)

dbSNP: rs1060502341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000456385 SCV000549335 uncertain significance Hereditary breast ovarian cancer syndrome 2020-01-11 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces leucine with proline at codon 574 of the BRCA1 protein (p.Leu574Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 409328). 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 RCV000569485 SCV000665883 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-12 criteria provided, single submitter clinical testing The p.L574P variant (also known as c.1721T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 1721. The leucine at codon 574 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283889 SCV001469372 uncertain significance not provided 2020-08-26 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000569485 SCV003851083 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).

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