ClinVar Miner

Submissions for variant NM_015915.5(ATL1):c.1040T>C (p.Met347Thr)

dbSNP: rs1595620366
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000993058 SCV001145766 uncertain significance not provided 2019-01-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003311931 SCV004297093 pathogenic Hereditary spastic paraplegia 3A 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 347 of the ATL1 protein (p.Met347Thr). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met347 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21321493, 25637064). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt ATL1 protein function. ClinVar contains an entry for this variant (Variation ID: 805504). This missense change has been observed in individuals with autosomal dominant hereditary spastic paraplegia (PMID: 21321493, 25637064). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
Inherited Neuropathy Consortium Ii, University Of Miami RCV003311931 SCV004011931 uncertain significance Hereditary spastic paraplegia 3A 2016-01-06 no assertion criteria provided literature only

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