Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001051505 | SCV001215661 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2O | 2024-04-04 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 592 of the DYNC1H1 protein (p.Phe592Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 847870). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DYNC1H1 protein function with a negative predictive value of 95%. 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. |
| Illumina Laboratory Services, |
RCV001249746 | SCV001423779 | uncertain significance | DYNC1H1-related neurodevelopmental disorders | 2020-04-01 | criteria provided, single submitter | clinical testing | The DYNC1H1 c.1774T>C (p.Phe592Leu) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequence coverage so the variant is presumed to be rare. The p.Phe592Leu variant is located in the DYNC1H1 binding domain which is important for dynein complex formation (Hoang et al. 2017). Based on the limited evidence, the p.Phe592Leu is classified as a variant of unknown significance for autosomal dominant DYNC1H1-related neurodevelopmental disorders. |
| Gene |
RCV003117727 | SCV003798633 | uncertain significance | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28196890, 26100331, 25512093, 25609763) |