Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022553 | SCV001184305 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-23 | criteria provided, single submitter | clinical testing | The p.C1494S variant (also known as c.4480T>A), located in coding exon 29 of the ATM gene, results from a T to A substitution at nucleotide position 4480. The cysteine at codon 1494 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly 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 | RCV001037741 | SCV001201169 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-12-16 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 cysteine with serine at codon 1494 of the ATM protein (p.Cys1494Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. |