Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001216916 | SCV001388737 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-04-28 | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 2371 of the ATM protein (p.Tyr2371Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Ambry Genetics | RCV003294044 | SCV004007236 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-19 | criteria provided, single submitter | clinical testing | The p.Y2371C variant (also known as c.7112A>G), located in coding exon 48 of the ATM gene, results from an A to G substitution at nucleotide position 7112. The tyrosine at codon 2371 is replaced by cysteine, an amino acid with highly dissimilar 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. |