ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4133C>T (p.Pro1378Leu) (rs750771205)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213085 SCV000273990 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Color RCV000213085 SCV000682187 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-20 criteria provided, single submitter clinical testing
Invitae RCV000539074 SCV000622475 uncertain significance Ataxia-telangiectasia syndrome 2017-09-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1378 of the ATM protein (p.Pro1378Leu). The leucine residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. While this variant is not present in population databases (rs750771205), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 230438). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this sequence change is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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