ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.382G>A (p.Val128Met) (rs587779835)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115180 SCV000149089 uncertain significance not specified 2014-01-17 criteria provided, single submitter clinical testing This variant is denoted ATM c.382G>A at the cDNA level, p.Val128Met (V128M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val128Met 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. This variant is a conservative substitution of one neutral non-polar amino acid for another, altering a position that is moderately conserved throughout evolution and is not located in a known functional domain. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on currently available information, it is unclear whether ATM Val128Met is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000476476 SCV000546770 uncertain significance Ataxia-telangiectasia syndrome 2016-07-01 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 128 of the ATM protein (p.Val128Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127375). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000566741 SCV000672701 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000476476 SCV000793989 uncertain significance Ataxia-telangiectasia syndrome 2017-11-14 criteria provided, single submitter clinical testing

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