Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002225240 | SCV002503853 | uncertain significance | Autosomal dominant cerebellar ataxia | 2020-11-30 | criteria provided, single submitter | clinical testing | This sequence change is predicted to replace arginine with cysteine at codon 233 of the MTCL1 protein (p.(Arg233Cys)). The arginine residue is highly conserved (100 vertebrates, UCSC), and is located in the coiled coil domain (PMID: 23902687). There is a large physicochemical difference between arginine and cysteine. The variant is present in a large population cohort at a frequency of 0.002% (rs758581749, 4/248,576 alleles, 0 homozygotes in gnomAD v2.1), and has not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (5/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.3.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PP3. |