Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207766 | SCV001379132 | likely pathogenic | Amyotrophic lateral sclerosis type 10; TARDBP-related frontotemporal dementia | 2022-07-25 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 938527). This missense change has been observed in individuals with amyotrophic lateral sclerosis and/or clinical features of amyotrophic lateral sclerosis (PMID: 32253937; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 321 of the TARDBP protein (p.Ala321Asp). This variant disrupts the p.Ala231 amino acid residue in TARDBP. Other variant(s) that disrupt this residue have been observed in individuals with TARDBP-related conditions (PMID: 19760257, 19864663, 32253937), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |