ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8717T>C (p.Val2906Ala) (rs730881328)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159664 SCV000209662 uncertain significance not provided 2015-03-09 criteria provided, single submitter clinical testing This variant is denoted ATM c.8717T>C at the cDNA level, p.Val2906Ala (V2906A) at the protein level, and results in the change of a Valine to an Alanine (GTT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val2906Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Alanine share similar properties, this is considered a conservative amino acid substitution. ATM Val2906Ala occurs at a position that is well conserved across species and is located in the PI3K/PI4K domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Val2906Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000628195 SCV000749088 uncertain significance Ataxia-telangiectasia syndrome 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 2906 of the ATM protein (p.Val2906Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs730881328, ExAC 0.001%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 181901). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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