Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213831 | SCV001385481 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-06-29 | criteria provided, single submitter | clinical testing | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant is present in population databases (rs748431827, ExAC 0.02%). This sequence change replaces histidine with arginine at codon 553 of the BRCA1 protein (p.His553Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001732072 | SCV001983626 | uncertain significance | not specified | 2021-09-19 | criteria provided, single submitter | clinical testing | |
University of Washington Department of Laboratory Medicine, |
RCV003158496 | SCV003851141 | 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). |