ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3731A>T (p.His1244Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003036252 SCV003352178 uncertain significance Hereditary breast ovarian cancer syndrome 2022-09-13 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. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1244 of the BRCA1 protein (p.His1244Leu).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157932 SCV003849896 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).
Ambry Genetics RCV003157932 SCV005547443 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-13 criteria provided, single submitter clinical testing The p.H1244L variant (also known as c.3731A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3731. The histidine at codon 1244 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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