Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000810038 | SCV000950224 | pathogenic | Hereditary spastic paraplegia 3A | 2022-07-11 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with hereditary spastic paraplegia (Invitae). In at least one individual the variant was observed to be de novo. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 350 of the ATL1 protein (p.Ala350Thr). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 654142). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Ala350 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been observed in individuals with ATL1-related conditions (PMID: 29980238), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |