ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1978G>A (p.Val660Ile)

dbSNP: rs876660889
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214150 SCV000278676 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-16 criteria provided, single submitter clinical testing The p.V660I variant (also known as c.1978G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1978. The valine at codon 660 is replaced by isoleucine, an amino acid with highly 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.
Color Diagnostics, LLC DBA Color Health RCV000214150 SCV000688358 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-06 criteria provided, single submitter clinical testing
Invitae RCV001040287 SCV001203850 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 660 of the BRCA1 protein (p.Val660Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 34981296). ClinVar contains an entry for this variant (Variation ID: 234157). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000214150 SCV003849588 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).
BRCAlab, Lund University RCV003493534 SCV004244106 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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