Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000527186 | SCV000622624 | uncertain significance | Ataxia-telangiectasia syndrome | 2017-02-05 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. This sequence change replaces lysine with arginine at codon 1964 of the ATM protein (p.Lys1964Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. In summary, this variant is a novel missense change that is not predicted to affect protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002358422 | SCV002653608 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-16 | criteria provided, single submitter | clinical testing | The p.K1964R variant (also known as c.5891A>G), located in coding exon 38 of the ATM gene, results from an A to G substitution at nucleotide position 5891. The lysine at codon 1964 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well 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. |
Gene |
RCV004760550 | SCV005371587 | uncertain significance | not provided | 2023-06-29 | 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176) |