Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003526067 | SCV004330749 | uncertain significance | Welander distal myopathy | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 381 of the TIA1 protein (p.Ala381Thr). This variant is present in population databases (rs768554955, gnomAD 0.002%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis and/or frontotemporal dementia (PMID: 29216908, 29886022). ClinVar contains an entry for this variant (Variation ID: 992596). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects TIA1 function (PMID: 28817800, 36112647). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV001281090 | SCV001468514 | pathogenic | Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia | 2021-01-06 | no assertion criteria provided | literature only |