ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5204C>T (p.Thr1735Ile)

dbSNP: rs1555105650
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001820656 SCV002068135 uncertain significance not specified 2020-05-27 criteria provided, single submitter clinical testing DNA sequence analysis of the ATM gene demonstrated a sequence change, c.5204C>T, in exon 35 that results in an amino acid change, p.Thr1735Ile. This sequence change does not appear to have been previously described in patients with ATM-related disorders and has also not been described in population databased (gnomAD, ExAC). The p.Thr1735Ile change affects a poorly conserved amino acid residue located in a domain of the ATM protein that is known to be functional. The p.Thr1735Ile substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Thr1735Ile change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002545159 SCV003334814 uncertain significance Ataxia-telangiectasia syndrome 2022-03-23 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. 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. 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). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1735 of the ATM protein (p.Thr1735Ile).
Ambry Genetics RCV004040988 SCV005017734 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-13 criteria provided, single submitter clinical testing The p.T1735I variant (also known as c.5204C>T), located in coding exon 34 of the ATM gene, results from a C to T substitution at nucleotide position 5204. The threonine at codon 1735 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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.

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