Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000690424 | SCV000818108 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with proline at codon 2210 of the ATM protein (p.Gln2210Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. 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. |
Ambry Genetics | RCV002360737 | SCV002664509 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-31 | criteria provided, single submitter | clinical testing | The p.Q2210P variant (also known as c.6629A>C), located in coding exon 45 of the ATM gene, results from an A to C substitution at nucleotide position 6629. The glutamine at codon 2210 is replaced by proline, an amino acid with similar properties. This variant was observed in an individual with breast cancer amongst a cohort of 1781 non-Ashkenazi Jewish individuals undergoing BRCA1/2 gene testing based on a personal history of breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33).This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003231580 | SCV003929786 | uncertain significance | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Tung et al., 2015); This variant is associated with the following publications: (PMID: 23532176, 25186627) |