ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.8876A>G (p.Tyr2959Cys)

gnomAD frequency: 0.00001  dbSNP: rs797045536
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192315 SCV000247226 uncertain significance not specified 2014-05-06 criteria provided, single submitter clinical testing
Invitae RCV001852554 SCV002109554 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2022-05-14 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2959 of the DYNC1H1 protein (p.Tyr2959Cys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 210885). 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. 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.
Ambry Genetics RCV002444778 SCV002682782 uncertain significance Inborn genetic diseases 2020-03-19 criteria provided, single submitter clinical testing The p.Y2959C variant (also known as c.8876A>G), located in coding exon 45 of the DYNC1H1 gene, results from an A to G substitution at nucleotide position 8876. The tyrosine at codon 2959 is replaced by cysteine, an amino acid with highly dissimilar 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.

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