Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069903 | SCV001235101 | uncertain significance | Charcot-Marie-Tooth disease type 2R | 2021-04-16 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TRIM2-related conditions. This variant is present in population databases (rs113767540, ExAC 0.006%). This sequence change replaces isoleucine with leucine at codon 512 of the TRIM2 protein (p.Ile512Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. |
| Ambry Genetics | RCV002554593 | SCV003569634 | uncertain significance | Inborn genetic diseases | 2021-08-02 | criteria provided, single submitter | clinical testing | The c.1615A>T (p.I539L) alteration is located in exon 8 (coding exon 8) of the TRIM2 gene. This alteration results from a A to T substitution at nucleotide position 1615, causing the isoleucine (I) at amino acid position 539 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |