ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1152C>G (p.Cys384Trp)

gnomAD frequency: 0.00001  dbSNP: rs777755997
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233701 SCV000282863 uncertain significance Ataxia-telangiectasia syndrome 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 384 of the ATM protein (p.Cys384Trp). This variant is present in population databases (rs777755997, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 236668). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000575339 SCV000667885 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-22 criteria provided, single submitter clinical testing The p.C384W variant (also known as c.1152C>G), located in coding exon 8 of the ATM gene, results from a C to G substitution at nucleotide position 1152. The cysteine at codon 384 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000575339 SCV001344534 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-03 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tryptophan at codon 384 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000233701 SCV002092768 uncertain significance Ataxia-telangiectasia syndrome 2020-11-07 no assertion criteria provided clinical testing

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