ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.821C>T (p.Ser274Phe)

dbSNP: rs1591504377
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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 RCV000800834 SCV000940570 uncertain significance Ataxia-telangiectasia syndrome 2022-01-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 274 of the ATM protein (p.Ser274Phe). 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: 646532). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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 RCV002424847 SCV002678297 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-26 criteria provided, single submitter clinical testing The p.S274F variant (also known as c.821C>T), located in coding exon 6 of the ATM gene, results from a C to T substitution at nucleotide position 821. The serine at codon 274 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is not 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 RCV002424847 SCV004357912 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces serine with phenylalanine at codon 274 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). 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.
Baylor Genetics RCV004569571 SCV005057179 uncertain significance Familial cancer of breast 2023-12-01 criteria provided, single submitter clinical testing

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