Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489846 | SCV000577545 | likely benign | not provided | 2021-02-22 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25025039, 32376792) |
Labcorp Genetics |
RCV001083586 | SCV000642316 | likely benign | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000489846 | SCV001148357 | uncertain significance | not provided | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV001173342 | SCV001336430 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Mayo Clinic Laboratories, |
RCV000489846 | SCV001716100 | uncertain significance | not provided | 2020-12-18 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222528 | SCV002500219 | likely benign | not specified | 2022-03-08 | criteria provided, single submitter | clinical testing | Variant summary: IGHMBP2 c.165G>C (p.Gln55His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00058 in 251490 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in IGHMBP2 causing Charcot-Marie-Tooth Disease, Axonal, Type 2S, allowing no conclusion about variant significance. Although reported as a VUS in settings of multigene panel testing among cohorts of individuals with suspected Charcot-Marie-Tooth (CMT) disease (example, Volodarsky_2021), to our knowledge, no penetrant association of c.165G>C in individuals affected with Charcot-Marie-Tooth Disease, Axonal, Type 2S and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV002404282 | SCV002707523 | uncertain significance | Inborn genetic diseases | 2022-05-10 | criteria provided, single submitter | clinical testing | The p.Q55H variant (also known as c.165G>C), located in coding exon 2 of the IGHMBP2 gene, results from a G to C substitution at nucleotide position 165. The glutamine at codon 55 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Revvity Omics, |
RCV000489846 | SCV003813341 | uncertain significance | not provided | 2020-01-10 | criteria provided, single submitter | clinical testing |