Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000543924 | SCV000622565 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1703 of the ATM protein (p.Phe1703Ser). This variant is present in population databases (rs772376652, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 453560). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Color Diagnostics, |
RCV000777913 | SCV000913951 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000777913 | SCV003866539 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-28 | criteria provided, single submitter | clinical testing | The p.F1703S variant (also known as c.5108T>C), located in coding exon 33 of the ATM gene, results from a T to C substitution at nucleotide position 5108. The phenylalanine at codon 1703 is replaced by serine, an amino acid with highly dissimilar properties. This alteration was observed with an allele frequency of 0 in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry. In addition, it was not observed in unselected male breast cancer patients and was observed with an allele frequency of 0 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun. 2018 Oct;9:4083). This amino acid position is not 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. |
| Baylor Genetics | RCV003470672 | SCV004210071 | uncertain significance | Familial cancer of breast | 2023-08-05 | criteria provided, single submitter | clinical testing |