ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.925A>G (p.Lys309Glu)

gnomAD frequency: 0.00001  dbSNP: rs200079527
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001810993 SCV000604014 uncertain significance not provided 2019-11-11 criteria provided, single submitter clinical testing The IGHMBP2 c.925A>G; p.Lys309Glu variant (rs200079527), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 439817). This variant is found on only seven chromosomes (7/251390 alleles) in the Genome Aggregation Database. The lysine at codon 309 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Lys309Glu variant is uncertain at this time.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173340 SCV001336428 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001368198 SCV001564583 uncertain significance Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 309 of the IGHMBP2 protein (p.Lys309Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs200079527, ExAC 0.008%). 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: 439817). 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.
Ambry Genetics RCV002376941 SCV002684303 uncertain significance Inborn genetic diseases 2021-03-27 criteria provided, single submitter clinical testing The p.K309E variant (also known as c.925A>G), located in coding exon 7 of the IGHMBP2 gene, results from an A to G substitution at nucleotide position 925. The lysine at codon 309 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.