Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000808899 | SCV000949029 | likely pathogenic | Hereditary spastic paraplegia 31 | 2019-01-15 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the REEP1 gene (p.Pro172Hisfs*51). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acids of the REEP1 protein and extend the protein by an additional 21 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with REEP1-related disease. This variant disrupts the C-terminus of the REEP1 protein. Other variants that result in a similarly extended protein product (p.Gly180Leufs*38, p.Arg177Glyfs*46, p.Ser179Argfs*43) have been observed in families affected with hereditary spastic paraplegia (PMID: 16826527, 18321925, Invitae). This suggests that these extensions may be clinically significant. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |