ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3667C>G (p.Leu1223Val)

dbSNP: rs1555587309
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001225218 SCV001397459 uncertain significance Hereditary breast ovarian cancer syndrome 2022-10-04 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 952987). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 30702160). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1223 of the BRCA1 protein (p.Leu1223Val).
Ambry Genetics RCV002451530 SCV002615684 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-03 criteria provided, single submitter clinical testing The p.L1223V variant (also known as c.3667C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3667. The leucine at codon 1223 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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 RCV002451530 SCV003851615 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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