Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000196650 | SCV000251700 | likely benign | not specified | 2017-12-01 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Invitae | RCV001086652 | SCV000290025 | benign | Charcot-Marie-Tooth disease type 2 | 2024-01-30 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000312138 | SCV000347988 | likely benign | Hereditary motor and sensory neuropathy with optic atrophy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Ce |
RCV000487518 | SCV000574747 | likely benign | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | MFN2: BS2 |
| Athena Diagnostics | RCV000487518 | SCV000841605 | benign | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000002372 | SCV001135183 | benign | Charcot-Marie-Tooth disease type 2A2 | 2023-08-22 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000196650 | SCV001160434 | likely benign | not specified | 2019-03-02 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Laboratory, |
RCV001172693 | SCV001335759 | likely benign | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Practice for Gait Abnormalities, |
RCV001814957 | SCV002061902 | likely pathogenic | Tip-toe gait | 2021-03-17 | criteria provided, single submitter | clinical testing | The variant has been described in numerous publications in patients with symptoms of Charcot-Marie-Tooth disease (CMT) and has been detected in 3.4% of CMT families [Braathen (2010) BMC Med Genet 11: 48]. In 6 of 14 Spanish families, the variant was described in patients with mild to moderate CMT2 symptoms, which, however, only occurred in the 3rd-5th decade of life [Casasnovas (2010) J Med Genet 47: 249]. However, in a paper by Antoniadi published in 2015, the MFN-2 variant was also documented in two patients with symptoms of early CMT1 and Braathen et al. reported on a CMT1 patient with clinical manifestations in the 2nd year of life. [Antoniadi (2015) BMC Med Genet 16:84; Braathen (2010) BMC Med Genet 11:48]. Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth Disease (CMT), is the most commonly inherited peripheral polyneuropathy. It constitutes a group of inherited, progressive, motor and sensory peripheral nerve disorders with properties of demyelination, axonal degeneration, or both. It is classified by clinical characteristics, modes of inheritance, electrophysiologic features, metabolic defects, and specific gene markers. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed. |
| Ambry Genetics | RCV002390086 | SCV002699164 | likely benign | Inborn genetic diseases | 2021-08-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| OMIM | RCV000002372 | SCV000022530 | pathogenic | Charcot-Marie-Tooth disease type 2A2 | 2010-04-01 | flagged submission | literature only | |
| Eurofins Ntd Llc |
RCV000487518 | SCV000331380 | uncertain significance | not provided | 2015-11-19 | flagged submission | clinical testing |