ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.1757T>G (p.Val586Gly) (rs864622357)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757201 SCV000885342 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing The DYNC2H1 c.1757T>G; p.Val586Gly variant (rs864622357), to our knowledge, is not reported in the medical literature but is described as pathogenic by one laboratory in ClinVar (Variation ID: 220042). It is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The valine at codon 586 is highly conserved and computational algorithms (SIFT, PolyPhen-2) predict this variant to be deleterious. Due to limited information regarding this variant, its clinical significance cannot be determined with certainty.
Invitae RCV000206436 SCV000260277 pathogenic Jeune thoracic dystrophy 2015-08-28 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 586 of the DYNC2H1 protein (p.Val586Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant has not been published in the literature and is not present in population databases. Although this c.1757T>G (p.Val586Gly) variant has not been reported in the literature, a mutation in the neighboring codon c.1759C>T (p.Arg587Cys) has been reported to segregate with short-rib polydactyly syndrome in a single consanguineous family (PMID: 19361615). This variant was found in trans with a pathogenic variant in DYNC2H1 (c.2702+1G>A) in the proband of this family who was diagnosed with asphyxiating thoracic dystrophy. The phase of the two variants were confirmed through parental testing. For these reasons, this variant has been classified as Pathogenic.

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