Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001382565 | SCV001581405 | pathogenic | Hereditary spastic paraplegia 7 | 2022-06-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1070427). Disruption of the initiator codon has been observed in individuals with hereditary spastic paraplegia (PMID: 22964162, 23065789; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SPG7 mRNA. The next in-frame methionine is located at codon 44. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469389 | SCV002766219 | uncertain significance | not specified | 2022-11-26 | criteria provided, single submitter | clinical testing | Variant summary: SPG7 c.2T>A (p.Met1Lys) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. An alternative downstream in-frame start codon (Met44) is located in the encoded protein. An activation of this potential downstream translation initiation site would result in a shortened protein missing the first 43 amino acids from the protein sequence. To our knowledge no other pathogenic variants has been reported upstream of this alternate codon. Two of two in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 89584 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2T>A in individuals affected with Hereditary Spastic Paraplegia 7 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |