Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV000856963 | SCV001336669 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001320701 | SCV001511497 | uncertain significance | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2022-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 199 of the IGHMBP2 protein (p.Ala199Val). This variant is present in population databases (rs780802298, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 694854). 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 IGHMBP2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002538887 | SCV003753056 | uncertain significance | Inborn genetic diseases | 2022-04-14 | criteria provided, single submitter | clinical testing | The c.596C>T (p.A199V) alteration is located in exon 5 (coding exon 5) of the IGHMBP2 gene. This alteration results from a C to T substitution at nucleotide position 596, causing the alanine (A) at amino acid position 199 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genesis Genome Database | RCV000856963 | SCV000999528 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |