Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001211882 | SCV001383445 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2019-07-19 | 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 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 DYNC1H1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 4595 of the DYNC1H1 protein (p.Gln4595Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. |
Ambry Genetics | RCV002562378 | SCV003653598 | uncertain significance | Inborn genetic diseases | 2022-10-03 | criteria provided, single submitter | clinical testing | The c.13784A>G (p.Q4595R) alteration is located in exon 77 (coding exon 77) of the DYNC1H1 gene. This alteration results from a A to G substitution at nucleotide position 13784, causing the glutamine (Q) at amino acid position 4595 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |