Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000005291 | SCV000255847 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2013-06-24 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000236487 | SCV000292701 | pathogenic | not provided | 2018-04-27 | criteria provided, single submitter | clinical testing | The R315W missense pathogenic variant in the TRPV4 gene has been reported previously in association with scapuloperoneal spinal muscular atrophy and CMT2C with vocal cord paresis and short stature (Auer-Grumbach et al., 2010; Chen et al., 2010). Functional studies show that R315W alters the localization of the TRPV4 protein to the cell surface (Auer-Grumbach et al., 2010) and alters the channel function by increasing basal activity, leading to increased cell death (Inada et al., 2012). The R315W variant alters a highly conserved position predicted to be within the ankyrin repeat domain of the TRPV4 protein, where other missense pathogenic variants associated with CMT2C have been reported (Stenson et al., 2014). Therefore, the presence of the R315W pathogenic variant is consistent with a diagnosis of a TRPV4-related disorder |
Invitae | RCV000005291 | SCV000646256 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2019-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 315 of the TRPV4 protein (p.Arg315Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary motor and sensory neuropathy type 2C (HMSN2C), scapuloperoneal spinal muscular atrophy (SPSMA), Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis, and congenital distal SMA in several families (PMID: 20037588, 21115951, 20460441, 22065612). ClinVar contains an entry for this variant (Variation ID: 4999). Experimental studies have shown that this missense change reduces thermal stability, alters the localization of the TRPV4 protein to the cell surface, and leads to substantially higher basal calcium levels than wild type TRPV4 (PMID: 20037588, 22702953, 21454511). For these reasons, this variant has been classified as Pathogenic. |
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, |
RCV000005290 | SCV001251010 | likely pathogenic | Scapuloperoneal spinal muscular atrophy | 2020-03-31 | criteria provided, single submitter | research | |
OMIM | RCV000005289 | SCV000025467 | pathogenic | Distal spinal muscular atrophy, congenital nonprogressive | 2011-12-01 | no assertion criteria provided | literature only | |
OMIM | RCV000005290 | SCV000025468 | pathogenic | Scapuloperoneal spinal muscular atrophy | 2011-12-01 | no assertion criteria provided | literature only | |
OMIM | RCV000005291 | SCV000025469 | pathogenic | Charcot-Marie-Tooth disease axonal type 2C | 2011-12-01 | no assertion criteria provided | literature only | |
Gene |
RCV000202514 | SCV000148064 | pathogenic | Neuromuscular disease | 2014-04-02 | no assertion criteria provided | literature only | |
Gene |
RCV000192244 | SCV000239892 | pathogenic | Charcot-Marie-Tooth disease | 2015-04-30 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000789585 | SCV000928941 | uncertain significance | Autosomal dominant distal hereditary motor neuropathy | no assertion criteria provided | literature only |