ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.10522C>A (p.Leu3508Ile) (rs149496322)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717735 SCV000848593 uncertain significance History of neurodevelopmental disorder 2017-07-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Athena Diagnostics Inc RCV000711517 SCV000841894 likely benign not provided 2018-06-13 criteria provided, single submitter clinical testing
GeneDx RCV000430861 SCV000518425 likely benign not specified 2016-12-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000461707 SCV000548832 uncertain significance Charcot-Marie-Tooth disease, axonal, type 2O 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 3508 of the DYNC1H1 protein (p.Leu3508Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs149496322, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). 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: "Probably 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.

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