Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523142 | SCV000619427 | uncertain significance | not provided | 2017-07-31 | criteria provided, single submitter | clinical testing | The L4113S variant in the DYNC2H1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L4113S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L4113S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret L4113S as a variant of uncertain significance. |
ARUP Laboratories, |
RCV001803813 | SCV002047913 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 2021-07-16 | criteria provided, single submitter | clinical testing | The DYNC2H1 c.12338T>C; p.Leu4113Ser variant (rs369591902), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on four allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The leucine at codon 4113 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.427). Due to limited information, the clinical significance of the p.Leu4113Ser variant is uncertain at this time. |