ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5746A>G (p.Met1916Val) (rs910274159)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561900 SCV000660543 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-07 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001056111 SCV001220532 uncertain significance Ataxia-telangiectasia syndrome 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1916 of the ATM protein (p.Met1916Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with colorectal cancer (Invitae). However, in that individual pathogenic allele[s] were also identified in ATM, which suggests that this c.5746A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 478951). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. 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.

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