Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001004861 | SCV001164339 | likely pathogenic | Autosomal recessive spinocerebellar ataxia 17 | 2018-12-03 | criteria provided, single submitter | research | The homozygous p.Lys387GlufsTer3 variant in CWF19L1 was identified by our study in one individual with Spinocerebellar Ataxia. The p.Lys387GlufsTer3 variant in CWF19L1 has not been previously reported in individuals with spinocerebellar ataxia and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 387 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. A knock-out zebrafish model for the CWF19L1 gene has a phenotype that matches spinocerebellar ataxia and at least two loss of function variants across multiple exons have been reported in association with spinocerebellar ataxiain the literature (PMID: 25361784, 27016154, 26197978). Loss of function of the CWF19L1 gene is a moderately established disease mechanism in autosomal recessive Spinocerebellar Ataxia. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1_Strong (Richards 2015). |