Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002598340 | SCV002953370 | uncertain significance | Hereditary spastic paraplegia 4 | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 1917540). Disruption of the initiator codon has been observed in individual(s) with clinical features of SPAST-related conditions (PMID: 30476002). This sequence change affects the initiator methionine of the SPAST mRNA. The next in-frame methionine is located at codon 87. This variant disrupts a region of the SPAST protein in which other variant(s) (p.Glu43Gln) have been observed in individuals with SPAST-related conditions (PMID: 16055926). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |