ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1031C>T (p.Ala344Val)

dbSNP: rs876658636
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223230 SCV000274153 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-02 criteria provided, single submitter clinical testing The p.A344V variant (also known as c.1031C>T and 1150C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1031. The alanine at codon 344 is replaced by valine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 105000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.A344V remains unclear.
Invitae RCV001238345 SCV001411149 uncertain significance Hereditary breast ovarian cancer syndrome 2021-11-04 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 230563). 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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 344 of the BRCA1 protein (p.Ala344Val). 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. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000223230 SCV003846217 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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