ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4040G>A (p.Arg1347Lys)

dbSNP: rs80357210
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191518 SCV001359354 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 1347 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 19491284). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV002247444 SCV002517952 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV001191518 SCV003846627 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).
Invitae RCV003644885 SCV004517517 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1347 of the BRCA1 protein (p.Arg1347Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 19491284). ClinVar contains an entry for this variant (Variation ID: 55081). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112231 SCV000144943 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2007-04-10 no assertion criteria provided clinical testing

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