Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000415401 | SCV000493018 | likely pathogenic | Pes cavus; Distal lower limb muscle weakness; Peripheral neuropathy | 2014-06-03 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000414916 | SCV000493036 | pathogenic | Decreased nerve conduction velocity; Distal muscle weakness; Hand muscle atrophy; Peripheral demyelination; Peripheral neuropathy | 2014-06-11 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV001196666 | SCV001367296 | pathogenic | Charcot-Marie-Tooth disease type 1F | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. |
Invitae | RCV000015073 | SCV001377432 | pathogenic | Charcot-Marie-Tooth disease type 2E | 2022-09-01 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with mixed axonal and demyelinating neuropathy (PMID: 12481988, 15111691, 19286384). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NEFL function (PMID: 16452125, 21168446). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 14029). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 22 of the NEFL protein (p.Pro22Ser). |
Ambry Genetics | RCV002362585 | SCV002659258 | pathogenic | Inborn genetic diseases | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.P22S pathogenic mutation (also known as c.64C>T), located in coding exon 1 of the NEFL gene, results from a C to T substitution at nucleotide position 64. The proline at codon 22 is replaced by serine, an amino acid with similar properties. This variant was found to segregate with autosomal dominant Charcot-Marie-Tooth disease in one multigenerational family (Georgiou DM et al. Neurogenetics, 2002 Oct;4:93-6). This alteration has also been detected in the heterozygous state in individuals with mixed demyelinating and axonal neuropathy (Fabrizi GM et al. Neurology, 2004 Apr;62:1429-31; Bhagavati S et al. J Clin Neurosci, 2009 Jun;16:830-1). Functional studies have shown that this alteration led to abnormal neurofilament assembly and recapitulates the neuropathy phenotype in a mouse model (Fabrizi GM et al. Neurology, 2004 Apr;62:1429-31; Dequen F et al. Hum Mol Genet, 2010 Jul;19:2616-29; Miao L et al. J Cell Sci, 2013 Jan;126:427-36; Stone EJ et al. Cytoskeleton (Hoboken), 2019 07;76:423-439). Based on the supporting evidence, this variant is expected to be causative of Charcot-Marie-Tooth (CMT) disease, type 1F/2E; however, its clinical significance for the autosomal recessive form of NEFL-related CMT is unclear. |
Athena Diagnostics Inc | RCV000057144 | SCV004229812 | pathogenic | not provided | 2022-12-20 | criteria provided, single submitter | clinical testing | This variant segregates with autosomal dominant CMT in multiple families. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 16452125, 23230147, 20421365, 21168446) |
OMIM | RCV000015073 | SCV000035329 | pathogenic | Charcot-Marie-Tooth disease type 2E | 2006-03-15 | no assertion criteria provided | literature only | |
Epithelial Biology; Institute of Medical Biology, |
RCV000057144 | SCV000088257 | not provided | not provided | no assertion provided | not provided | ||
Gene |
RCV000194357 | SCV000243953 | not provided | Charcot-Marie-Tooth disease type 1C | no assertion provided | literature only |