Submissions for variant NM_002180.3(IGHMBP2):c.1844G>A (p.Arg615His)

gnomAD frequency: 0.00019  dbSNP: rs201640213

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235293	SCV000293058	uncertain significance	not provided	2020-10-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32376792)
Invitae	RCV000551552	SCV000642327	likely benign	Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001112400	SCV001270057	uncertain significance	Autosomal recessive distal spinal muscular atrophy 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173562	SCV001336659	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411069	SCV002712664	uncertain significance	Inborn genetic diseases	2021-10-13	criteria provided, single submitter	clinical testing	The p.R615H variant (also known as c.1844G>A), located in coding exon 13 of the IGHMBP2 gene, results from a G to A substitution at nucleotide position 1844. The arginine at codon 615 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000235293	SCV003916752	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing	IGHMBP2: PM2, BP4