Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001977998 | SCV002265255 | uncertain significance | not provided | 2021-08-08 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces methionine with isoleucine at codon 365 of the TONSL protein (p.Met365Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs201856507, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with TONSL-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
Ambry Genetics | RCV004970687 | SCV005520051 | uncertain significance | Inborn genetic diseases | 2024-10-24 | criteria provided, single submitter | clinical testing | The c.1095G>A (p.M365I) alteration is located in exon 9 (coding exon 9) of the TONSL gene. This alteration results from a G to A substitution at nucleotide position 1095, causing the methionine (M) at amino acid position 365 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |