ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4336G>T (p.Val1446Phe)

dbSNP: rs1060501658
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000458330 SCV000547011 uncertain significance Ataxia-telangiectasia syndrome 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1446 of the ATM protein (p.Val1446Phe). 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. 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. ClinVar contains an entry for this variant (Variation ID: 407655). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV004022653 SCV005016959 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-28 criteria provided, single submitter clinical testing The p.V1446F variant (also known as c.4336G>T), located in coding exon 28 of the ATM gene, results from a G to T substitution at nucleotide position 4336. The valine at codon 1446 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004568004 SCV005057150 uncertain significance Familial cancer of breast 2023-12-13 criteria provided, single submitter clinical testing

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