ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1612_1613delinsTT (p.Ala538Leu)

dbSNP: rs2080163350
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001180394 SCV001345321 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with leucine at codon 538 of the ATM protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001875986 SCV002147038 uncertain significance Ataxia-telangiectasia syndrome 2022-01-08 criteria provided, single submitter clinical testing Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces alanine with leucine at codon 538 of the ATM protein (p.Ala538Leu). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and leucine. This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 921140).
Ambry Genetics RCV001180394 SCV002705245 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-24 criteria provided, single submitter clinical testing The c.1612_1613delGCinsTT variant (also known as p.A538L), located in coding exon 10 of the ATM gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 1612 to 1613. The alanine at codon 538 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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