ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5178T>G (p.Cys1726Trp)

gnomAD frequency: 0.00001  dbSNP: rs1446243372
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001068557 SCV001233676 uncertain significance Ataxia-telangiectasia syndrome 2021-04-27 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. 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: "Benign"; 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 tryptophan at codon 1726 of the ATM protein (p.Cys1726Trp). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tryptophan.
GeneDx RCV001760046 SCV001989014 uncertain significance not provided 2019-06-14 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002339342 SCV002641151 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-24 criteria provided, single submitter clinical testing The p.C1726W variant (also known as c.5178T>G) is located in coding exon 34 of the ATM gene. The cysteine at codon 1726 is replaced by tryptophan, an amino acid with highly dissimilar properties. This change occurs in the first base pair of coding exon 34. This amino acid position is not 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.
Natera, Inc. RCV001068557 SCV002080872 uncertain significance Ataxia-telangiectasia syndrome 2020-11-06 no assertion criteria provided clinical testing

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