ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.4049C>T (p.Pro1350Leu) (rs1131691955)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492926 SCV000583222 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing The P1350L variant in the DYNC1H1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P1350L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1350L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P1350L as a variant of uncertain significance.
Invitae RCV000649565 SCV000771394 uncertain significance Charcot-Marie-Tooth disease, axonal, type 2O 2017-10-18 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1350 of the DYNC1H1 protein (p.Pro1350Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline 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 disease. ClinVar contains an entry for this variant (Variation ID: 430424). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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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