Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061075 | SCV001225806 | pathogenic | Amyotrophic lateral sclerosis type 1 | 2022-05-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 85 of the SOD1 protein (p.Leu85Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 9506558, 20577002, 21329474, 22670878, 24325798, 25792239). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Leu84Phe. ClinVar contains an entry for this variant (Variation ID: 855744). 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 SOD1 protein function. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). For these reasons, this variant has been classified as Pathogenic. |