Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236229 | SCV000294081 | uncertain significance | not provided | 2017-05-30 | criteria provided, single submitter | clinical testing | The E2814D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. However, the E2814D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001231858 | SCV001404393 | likely benign | Charcot-Marie-Tooth disease axonal type 2O | 2024-01-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002444939 | SCV002679351 | uncertain significance | Inborn genetic diseases | 2022-06-13 | criteria provided, single submitter | clinical testing | The p.E2814D variant (also known as c.8442G>C), located in coding exon 42 of the DYNC1H1 gene, results from a G to C substitution at nucleotide position 8442. The glutamic acid at codon 2814 is replaced by aspartic acid, an amino acid with highly similar properties. Among a cohort of 448 patients with suspected inherited peripheral neuropathy, this alteration was detected in one patient with CMT2; however, limited information was provided (Antoniadi T et al. BMC Med Genet, 2015 Sep;16:84). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |