Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000767173 | SCV000251713 | uncertain significance | not provided | 2019-01-07 | criteria provided, single submitter | clinical testing | A variant of unknown significance has been identified in the MFN2 gene. It has been reported in families with axonal hereditary motor and sensory neuropathy; however, the authors concluded that C281S is either a benign variant or a pathogenic variant associated with autosomal recessive inheritance as it was identified in healthy relatives with normal electrophysiological examination (Brozkova et al., 2013). The C281S variant is observed in 24/9838 (0.2%) alleles from individuals of Ashkenazi Jewish background, (Lek et al., 2016). However, the C281S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth disease type 2A (Stenson et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. |
Athena Diagnostics Inc | RCV000199052 | SCV000614095 | likely benign | not specified | 2016-12-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001087915 | SCV000775857 | likely benign | Charcot-Marie-Tooth disease, type 2 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV001087915 | SCV001256163 | likely benign | Charcot-Marie-Tooth disease, type 2 | 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. |
Illumina Clinical Services Laboratory, |
RCV001099689 | SCV001256164 | uncertain significance | 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Molecular Genetics Laboratory, |
RCV001174298 | SCV001337430 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |