Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000201072 | SCV000255780 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2015-07-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000236739 | SCV000292874 | pathogenic | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32334137, 32301006, 26989944, 25547330, 24607769, Scalia2021[Review], 34129932, 31902012, 33943041, 22176143, 21611841, 33973728) |
Ambry Genetics | RCV000622699 | SCV000741123 | pathogenic | Inborn genetic diseases | 2015-11-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000201072 | SCV000832663 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 136 of the HSPB1 protein (p.Arg136Leu). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individuals with features of Charcot-Marie-Tooth, type 2 (CMT2) disease and distal hereditary motor neuropathy (dHMN) (PMID: 21611841, 22176143, 25547330, 26989944). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217230). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HSPB1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg136 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been observed in individuals with HSPB1-related conditions (PMID: 15122254, 20178975, 22521462), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Molecular Genetics Laboratory, |
RCV000789060 | SCV001337300 | pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Ce |
RCV000236739 | SCV002563957 | pathogenic | not provided | 2019-09-01 | criteria provided, single submitter | clinical testing | |
Inherited Neuropathy Consortium | RCV000789060 | SCV000928409 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |