Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001905714 | SCV002152506 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 428 of the TCTN1 protein (p.Arg428Trp). This variant is present in population databases (rs572643772, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1386191). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TCTN1 protein function with a positive predictive value of 80%. 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. |
Fulgent Genetics, |
RCV002490125 | SCV002793871 | uncertain significance | Joubert syndrome 13 | 2022-05-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002553491 | SCV003547310 | uncertain significance | Inborn genetic diseases | 2021-08-09 | criteria provided, single submitter | clinical testing | The c.1282C>T (p.R428W) alteration is located in exon 11 (coding exon 11) of the TCTN1 gene. This alteration results from a C to T substitution at nucleotide position 1282, causing the arginine (R) at amino acid position 428 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |