ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1019C>A (p.Ala340Asp)

dbSNP: rs730881387
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218921 SCV000275978 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-21 criteria provided, single submitter clinical testing The p.A340D variant (also known as c.1019C>A), located in coding exon 7 of the ATM gene, results from a C to A substitution at nucleotide position 1019. The alanine at codon 340 is replaced by aspartic acid, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 66000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.A340D remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001367304 SCV001563650 uncertain significance Ataxia-telangiectasia syndrome 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 340 of the ATM protein (p.Ala340Asp). This variant is not present in population databases (gnomAD no frequency). 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: 231970). 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.

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