Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023738 | SCV001185653 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-11 | criteria provided, single submitter | clinical testing | The p.L1737W variant (also known as c.5210T>G), located in coding exon 34 of the ATM gene, results from a T to G substitution at nucleotide position 5210. The leucine at codon 1737 is replaced by tryptophan, an amino acid with similar 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 | RCV001363145 | SCV001559245 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-06-04 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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. ClinVar contains an entry for this variant (Variation ID: 825553). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with tryptophan at codon 1737 of the ATM protein (p.Leu1737Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. |