Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002225225 | SCV002503815 | uncertain significance | Autosomal recessive spinocerebellar ataxia 17 | 2020-09-24 | criteria provided, single submitter | clinical testing | This sequence change is predicted to replace lysine with glutamic acid at codon 355 of the CWF19L1 protein (p.(Lys355Glu)). The lysine residue is evolutionarily conserved (100 vertebrates, UCSC), and is located in a region similar to Cwfj C-terminus 1. There is a small physicochemical difference between lysine and glutamic acid. The variant is present in a large population cohort at a frequency of 0.001%, which is consistent with a recessive condition (PM2; rs1176487325, 3/251,440 alleles, 0 homozygotes in gnomAD v2.1). The variant has not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (PP3; 5/6 algorithms). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2, PP3. |