ClinVar Miner

Submissions for variant NM_015915.5(ATL1):c.773A>T (p.His258Leu)

dbSNP: rs119476048
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001970209 SCV002240150 pathogenic Hereditary spastic paraplegia 3A 2021-03-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His258 ‚Äãamino acid residue in ATL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11685207). 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 not expected to disrupt ATL1 protein function. This variant has been observed in individual(s) with clinical features of autosomal dominant ATL1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with leucine at codon 258 of the ATL1 protein (p.His258Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine.

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