ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.3680G>A (p.Arg1227Gln)

dbSNP: rs2048071941
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001253406 SCV001429094 uncertain significance Intellectual disability, autosomal dominant 13 2018-03-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348851 SCV002619175 uncertain significance Inborn genetic diseases 2018-03-13 criteria provided, single submitter clinical testing The p.R1227Q variant (also known as c.3680G>A), located in coding exon 16 of the DYNC1H1 gene, results from a G to A substitution at nucleotide position 3680. The arginine at codon 1227 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003426021 SCV004117052 uncertain significance DYNC1H1-related disorder 2022-09-01 criteria provided, single submitter clinical testing The DYNC1H1 c.3680G>A variant is predicted to result in the amino acid substitution p.Arg1227Gln. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003642957 SCV004548446 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1227 of the DYNC1H1 protein (p.Arg1227Gln). 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: 976187). 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 expected to disrupt DYNC1H1 protein function with a positive 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.

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