Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001316971 | SCV001507613 | uncertain significance | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 879 of the IGHMBP2 protein (p.Thr879Met). This variant is present in population databases (rs17612126, gnomAD 0.02%). 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: 1017770). 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 not 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. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV001823196 | SCV002073183 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2S | criteria provided, single submitter | clinical testing | The missense variant p.T879M in IGHMBP2 (NM_002180.2) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.T879M variant is observed in 7/30,616 (0.0229%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between threonine and methionine. The p.T879M missense variant is predicted to be tolerated by both SIFT or PolyPhen2. The nucleotide c.2636 in IGHMBP2 is not conserved according to a GERP++ and PhyloP analysis of 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |