ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3965T>C (p.Leu1322Pro)

gnomAD frequency: 0.00001  dbSNP: rs786203306
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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 RCV000628053 SCV000748941 uncertain significance Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 1322 of the ATM protein (p.Leu1322Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
Ambry Genetics RCV001021541 SCV001183168 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-23 criteria provided, single submitter clinical testing The p.L1322P variant (also known as c.3965T>C), located in coding exon 25 of the ATM gene, results from a T to C substitution at nucleotide position 3965. The leucine at codon 1322 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Suma Genomics RCV000628053 SCV002097336 likely pathogenic Ataxia-telangiectasia syndrome criteria provided, single submitter clinical testing

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