ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.1774T>C (p.Phe592Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001051505 SCV001215661 uncertain significance Charcot-Marie-Tooth disease, axonal, type 2O 2019-03-13 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 592 of the DYNC1H1 protein (p.Phe592Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DYNC1H1-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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 Clinical Services Laboratory,Illumina 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.

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