ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.404C>G (p.Ala135Gly)

dbSNP: rs1555059254
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000627915 SCV000748799 uncertain significance Ataxia-telangiectasia syndrome 2017-10-10 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 135 of the ATM protein (p.Ala135Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, 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 disease. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001021746 SCV001183398 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-07 criteria provided, single submitter clinical testing The p.A135G variant (also known as c.404C>G), located in coding exon 4 of the ATM gene, results from a C to G substitution at nucleotide position 404. The alanine at codon 135 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly 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.

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