ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.3571C>T (p.Arg1191Cys)

gnomAD frequency: 0.00004  dbSNP: rs774198261
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228142 SCV000287114 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2023-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1191 of the DYNC1H1 protein (p.Arg1191Cys). This variant is present in population databases (rs774198261, gnomAD 0.004%). 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: 238999). 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.
GeneDx RCV000236103 SCV000294178 uncertain significance not provided 2019-04-08 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002516315 SCV003745378 uncertain significance Inborn genetic diseases 2022-11-21 criteria provided, single submitter clinical testing The c.3571C>T (p.R1191C) alteration is located in exon 16 (coding exon 16) of the DYNC1H1 gene. This alteration results from a C to T substitution at nucleotide position 3571, causing the arginine (R) at amino acid position 1191 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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