Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212782 | SCV001384379 | pathogenic | Spastic paraplegia | 2023-05-20 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 29126212). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP7B1 protein function. ClinVar contains an entry for this variant (Variation ID: 942745). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 321 of the CYP7B1 protein (p.Glu321Lys). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282486 | SCV002571870 | likely pathogenic | Hereditary spastic paraplegia | 2022-08-08 | criteria provided, single submitter | clinical testing | Variant summary: CYP7B1 c.961G>A (p.Glu321Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251118 control chromosomes (gnomAD). c.961G>A has been reported in the literature in trans with a pathogenic variant in at least four related individuals affected with Hereditary Spastic Paraplegia, Type 5a from an affected family in which the variant segregated with the disease phenotype (e.g. Burguez_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted an assessment for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genome |
RCV003483790 | SCV004228582 | not provided | Hereditary spastic paraplegia 5A; Congenital bile acid synthesis defect 3 | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 08-02-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |