Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001057647 | SCV001222150 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-01-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 433702). This sequence change replaces glutamine with arginine at codon 921 of the BRCA1 protein (p.Gln921Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. |
University of Washington Department of Laboratory Medicine, |
RCV003157600 | SCV003849362 | 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). |
Department of Pathology and Laboratory Medicine, |
RCV000501257 | SCV000591409 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Gln921Arg variant was not identified in the literature nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), HGMD, LOVD, COSMIC, UMD, or BIC databases. The p.Gln921 residue is conserved in mammals but not across lower organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance. |