ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.3121A>T (p.Met1041Leu)

dbSNP: rs867890249
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000649547 SCV000771376 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2020-09-15 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DYNC1H1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 1041 of the DYNC1H1 protein (p.Met1041Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine.
GeneDx RCV004773074 SCV005386166 uncertain significance not provided 2024-02-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25512093, 25609763, 26100331)
Ambry Genetics RCV004972818 SCV005576506 uncertain significance Inborn genetic diseases 2024-08-01 criteria provided, single submitter clinical testing The c.3121A>T (p.M1041L) alteration is located in exon 12 (coding exon 12) of the DYNC1H1 gene. This alteration results from a A to T substitution at nucleotide position 3121, causing the methionine (M) at amino acid position 1041 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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