Submissions for variant NM_002180.3(IGHMBP2):c.181G>C (p.Gly61Arg)

gnomAD frequency: 0.00001  dbSNP: rs1057518943

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698226	SCV000826878	likely pathogenic	Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S	2023-08-28	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 61 of the IGHMBP2 protein (p.Gly61Arg). This variant is present in population databases (no rsID available, gnomAD 0.002%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IGHMBP2 protein function. ClinVar contains an entry for this variant (Variation ID: 575884). This missense change has been observed in individuals with IGHMBP2-related conditions (Invitae). It has also been observed to segregate with disease in related individuals.
Ambry Genetics	RCV002406605	SCV002713096	uncertain significance	Inborn genetic diseases	2021-03-03	criteria provided, single submitter	clinical testing	The p.G61R variant (also known as c.181G>C), located in coding exon 2 of the IGHMBP2 gene, results from a G to C substitution at nucleotide position 181. The glycine at codon 61 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572867	SCV001797901	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001572867	SCV001807871	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001572867	SCV001953591	uncertain significance	not provided		no assertion criteria provided	clinical testing