ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1030G>A (p.Ala344Thr)

gnomAD frequency: 0.00001  dbSNP: rs79727659
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000581734 SCV000688312 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-22 criteria provided, single submitter clinical testing
Counsyl RCV000111530 SCV000785549 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-11-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985363 SCV001133474 uncertain significance not provided 2019-02-28 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000008 (2/251244 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In a large-scale breast cancer association study, the variant was observed in an individual with breast cancer as well as in unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA2)). This variant co-occurred with a pathogenic variant in the BRCA1 gene in individuals from our internal patient population, suggesting it may not be the primary cause of disease. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Invitae RCV001327254 SCV001518320 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 344 of the BRCA1 protein (p.Ala344Thr). This variant is present in population databases (rs79727659, gnomAD 0.002%). This missense change has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 16267036). ClinVar contains an entry for this variant (Variation ID: 54104). 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 RCV000581734 SCV002696339 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-25 criteria provided, single submitter clinical testing The p.A344T variant (also known as c.1030G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1030. The alanine at codon 344 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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 RCV000581734 SCV003846219 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).
Breast Cancer Information Core (BIC) (BRCA1) RCV000111530 SCV000143985 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2003-12-23 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000111530 SCV004244139 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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