Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000518873 | SCV000618509 | uncertain significance | not specified | 2017-06-20 | criteria provided, single submitter | clinical testing | The F40L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The F40L variant is observed in 12/10236 (0.12%) alleles from individuals of African background, in large population cohorts, and was observed in the homozygous state in 2 unrelated, presumably healthy individuals undergoing testing at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F40L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000871430 | SCV001013091 | likely benign | Hereditary sensory and autonomic neuropathy type 1 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
| Illumina Clinical Services Laboratory, |
RCV001249820 | SCV001329545 | benign | Neuropathy, hereditary sensory and autonomic, type 1A | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Molecular Genetics Laboratory, |
RCV001174074 | SCV001337194 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |