ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1436A>G (p.Asp479Gly) (rs1555070958)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567124 SCV000665379 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000590526 SCV000694183 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing Variant summary: The ATM c.1436A>G (p.Asp479Gly) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant. This variant is absent in 121338 control chromosomes and has been reported in one patient with breast cancer, without strong evidence for causality. Due to lack of clinical and functional evidence, this variant is classified as VUS.
Invitae RCV000627958 SCV000748844 uncertain significance Ataxia-telangiectasia syndrome 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 479 of the ATM protein (p.Asp479Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family affected with breast and/or ovarian cancer (PMID: 12810666). 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, 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.
Color RCV000567124 SCV001339873 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196372 SCV001366979 uncertain significance Seizures; EEG abnormality; Febrile seizures; Specific learning disability 2019-11-14 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2. This variant was detected in heterozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197304 SCV001367967 uncertain significance Hypogonadotropic hypogonadism 7 with or without anosmia; Neoplasm of the pancreas; Breast carcinoma; Decreased testosterone in males; Stomach cancer 2019-05-20 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM2,PM3,PP3. This variant was detected in heterozygous state.

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