ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3832G>A (p.Asp1278Asn) (rs730881365)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159718 SCV000209730 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing This variant is denoted ATM c.3832G>A at the cDNA level, p.Asp1278Asn (D1278N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAC>AAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asp1278Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Asp1278Asn occurs at a position that is not conserved and is not located in a known functional domain (Tavtigian 2009, Stracker 2013). 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 Asp1278Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000234345 SCV000282943 uncertain significance Ataxia-telangiectasia syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1278 of the ATM protein (p.Asp1278Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 181951). 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. 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.
Ambry Genetics RCV000566259 SCV000667863 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000234345 SCV000794783 uncertain significance Ataxia-telangiectasia syndrome 2017-10-17 criteria provided, single submitter clinical testing

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