ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.10241A>G (p.Asn3414Ser)

gnomAD frequency: 0.00001  dbSNP: rs1555411393
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622366 SCV000741449 uncertain significance Inborn genetic diseases 2016-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Invitae RCV001868142 SCV002203123 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2023-04-20 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3414 of the DYNC1H1 protein (p.Asn3414Ser). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYNC1H1 protein function. ClinVar contains an entry for this variant (Variation ID: 521041).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317300 SCV004020830 uncertain significance not specified 2023-06-07 criteria provided, single submitter clinical testing Variant summary: DYNC1H1 c.10241A>G (p.Asn3414Ser) results in a conservative amino acid change located in the Dynein heavy chain, tail (IPR013594) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251432 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10241A>G in individuals affected with DYNC1H1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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