Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002761523 | SCV003023247 | uncertain significance | Amyotrophic lateral sclerosis type 10; TARDBP-related frontotemporal dementia | 2022-04-28 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 352 of the TARDBP protein (p.Asn352Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TARDBP-related conditions. 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 tolerated. This variant disrupts the p.Asn352 amino acid residue in TARDBP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18779421, 22406069, 23327806, 24117534, 24237396, 24440310). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Ambry Genetics | RCV004067954 | SCV004962607 | uncertain significance | Inborn genetic diseases | 2023-11-30 | criteria provided, single submitter | clinical testing | The c.1054A>G (p.N352D) alteration is located in exon 6 (coding exon 5) of the TARDBP gene. This alteration results from a A to G substitution at nucleotide position 1054, causing the asparagine (N) at amino acid position 352 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |