ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.400G>A (p.Gly134Ser) (rs2234998)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476735 SCV000546747 uncertain significance Ataxia-telangiectasia syndrome 2018-08-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 134 of the ATM protein (p.Gly134Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs2234998, ExAC 0.02%). 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: 133632). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000571088 SCV000668053 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Fulgent Genetics,Fulgent Genetics RCV000764934 SCV000896106 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000120157 SCV000084298 not provided not specified 2013-09-19 no assertion provided reference population

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