Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021053 | SCV001182618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | The p.C1251Y variant (also known as c.3752G>A), located in coding exon 25 of the ATM gene, results from a G to A substitution at nucleotide position 3752. The cysteine at codon 1251 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is 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. |
Invitae | RCV001223387 | SCV001395534 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-01-27 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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. ClinVar contains an entry for this variant (Variation ID: 824161). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1251 of the ATM protein (p.Cys1251Tyr). |