Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000627617 | SCV000748617 | likely pathogenic | not provided | 2018-04-16 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the SPG7 gene. The c.2070delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2070delC variant causes a frameshift starting with codon Phenylalanine 691, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Phe691SerfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2070delC variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Paris Brain Institute, |
RCV001380103 | SCV001451065 | pathogenic | Hereditary spastic paraplegia 7 | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV001380103 | SCV001578049 | pathogenic | Hereditary spastic paraplegia 7 | 2020-01-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant has not been reported in the literature in individuals with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 524121). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe691Serfs*8) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. |