Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000201019 | SCV000255808 | pathogenic | Charcot-Marie-Tooth disease, type IA | 2014-07-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000638170 | SCV000759656 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu145Argfs*10) in the PMP22 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the PMP22 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with hereditary neuropathy with liability to pressure palsy (HNPP) (PMID: 21149811, 21252112, 23965407). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217238). For these reasons, this variant has been classified as Pathogenic. |
Centre for Mendelian Genomics, |
RCV001198269 | SCV001369148 | pathogenic | Roussy-Lévy syndrome | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. |
Genetics and Molecular Pathology, |
RCV000201019 | SCV002556845 | pathogenic | Charcot-Marie-Tooth disease, type IA | 2022-06-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002327053 | SCV002627911 | likely pathogenic | Inborn genetic diseases | 2020-05-22 | criteria provided, single submitter | clinical testing | The c.434delT variant, located in coding exon 4 of the PMP22 gene, results from a deletion of one nucleotide at nucleotide position 434, causing a translational frameshift with a predicted alternate stop codon (p.L145Rfs*10). Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of PMP22, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 16 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time. This variant has been reported in several families with hereditary neuropathy with liability to pressure palsies (HNPP) (Taioli F et al. Brain, 2011 Feb;134:608-17; Benedetti S et al. Arch. Neurol., 2010 Dec;67:1498-505; Beydoun SR et al. J Clin Neuromuscul Dis, 2013 Sep;15:28-33; Manganelli F et al. J. Peripher. Nerv. Syst., 2014 Dec;19:292-8) and in families with other inherited neuropathy syndromes, including Charcot-Marie-Tooth disease (Vaeth S et al. Eur J Med Genet, 2019 Jan;62:1-8; Lerat J et al. Mol Genet Genomic Med, 2019 09;7:e839; Simpson BS et al. J Clin Neuromuscul Dis, 2010 Jun;11:187-90). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Gene |
RCV003328564 | SCV004035680 | likely pathogenic | not provided | 2023-09-17 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 16 amino acids are replaced with 9 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23965407, 21149811, 32719652, 31393079, 29653220, 21252112) |