Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Lab, |
RCV000497541 | SCV000590825 | likely pathogenic | not provided | 2016-04-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000023430 | SCV000767281 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2017-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 316 of the TRPV4 protein (p.Arg316His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease type 2C (CMT2C), scapuloperoneal spinal muscular atrophy (SPSMA), distal hereditary motor neuropathy (dHMN), and arthrogryposis multiplex congenita (AMC) (PMID: 21288981, 24789864, 24319099). In one affected individual it was reported to occur de novo (PMID: 21288981) and in an affected family it was reported to segregate with disease (PMID: 24319099). ClinVar contains an entry for this variant (Variation ID: 30473). Experimental studies have shown that this missense change leads to cell death that can be reversed by a TRPV4 agonist (PMID: 21288981). A different missense substitution at this codon (p.Arg316Cys) has been determined to be pathogenic (PMID: 20037587, 20037588, 24789864, 21454511). This suggests that the arginine residue is critical for TRPV4 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |
Centre for Mendelian Genomics, |
RCV000023430 | SCV001368140 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. |
OMIM | RCV000023430 | SCV000044721 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2011-03-08 | no assertion criteria provided | literature only | |
Gene |
RCV000202476 | SCV000148066 | pathogenic | Neuromuscular disease | 2014-04-02 | no assertion criteria provided | literature only | |
Centre for Mendelian Genomics, |
RCV000415397 | SCV000492580 | pathogenic | Clubfoot; EMG abnormality; Lower limb amyotrophy | 2016-03-18 | no assertion criteria provided | clinical testing | |
Genesis Genome Database | RCV000856932 | SCV000999496 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |