Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012446 | SCV001172897 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-20 | criteria provided, single submitter | clinical testing | The p.C541Y variant (also known as c.1622G>A), located in coding exon 10 of the ATM gene, results from a G to A substitution at nucleotide position 1622. The cysteine at codon 541 is replaced by tyrosine, an amino acid with highly dissimilar properties. 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. |
Invitae | RCV001860710 | SCV002197905 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-03-27 | 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. 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. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 819680). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 541 of the ATM protein (p.Cys541Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |
Baylor Genetics | RCV003467602 | SCV004210126 | uncertain significance | Familial cancer of breast | 2023-07-24 | criteria provided, single submitter | clinical testing |