ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4784A>G (p.Asn1595Ser) (rs777812804)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231590 SCV000282968 uncertain significance Ataxia-telangiectasia syndrome 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1595 of the ATM protein (p.Asn1595Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs777812804, ExAC 0.001%). This variant has been reported in an individual affected with breast cancer (PMID: 20305132). ClinVar contains an entry for this variant (Variation ID: 236723). 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 RCV000575403 SCV000665200 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000575403 SCV000682222 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586254 SCV000694292 uncertain significance not provided 2016-09-26 criteria provided, single submitter clinical testing Variant summary: The ATM c.4784A>G (p.Asn1595Ser) variant involves the alteration of a conserved nucleotide and results in a replacement of a medium size and polar Asparagine (N) with a small size and polar Serine (S) located outside of known functional domains (InterPro, Pfam). 3/3 in silico tools predict a benign outcome for this substitution (SNPs&GO and Mutation taster not captured due to low reliability index). This variant was found in 1/121324 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). To our knowledge, the variant has not been reported in affected patients with strong evidence for causality and studies assessing the impact the variant may have on the function of ATM protein have not been published at the time of classification either. One clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
GeneKor MSA RCV000575403 SCV000821857 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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