Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000622734 | SCV000742302 | pathogenic | Inborn genetic diseases | 2017-03-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001009218 | SCV001169037 | likely pathogenic | not provided | 2019-03-15 | criteria provided, single submitter | clinical testing | The c.263dupG variant in the B4GALNT1 gene has been reported previously in the homozygous state in an individual with hereditary spastic paraplegia with learning disability, lower limb spasticity and weakness, nystagmus, axonal sensitive neuropathy, white matter hyperintensities, and cerebral atrophy (Boukhris et al., 2013). The c.263dupG variant causes a frameshift starting with codon Leucine 89, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Leu89ProfsX13. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.263dupG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.263dupG as a likely pathogenic variant. |
Knight Diagnostic Laboratories, |
RCV000054421 | SCV001448891 | pathogenic | Hereditary spastic paraplegia 26 | 2019-02-22 | criteria provided, single submitter | clinical testing | |
Genomics England Pilot Project, |
RCV000054421 | SCV001760310 | pathogenic | Hereditary spastic paraplegia 26 | criteria provided, single submitter | clinical testing | ||
Invitae | RCV002515735 | SCV003288334 | pathogenic | Spastic paraplegia | 2023-03-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 60525). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23746551, 32214227). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Leu89Profs*13) in the B4GALNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in B4GALNT1 are known to be pathogenic (PMID: 23746551). |
Baylor Genetics | RCV000054421 | SCV004183453 | pathogenic | Hereditary spastic paraplegia 26 | 2023-10-27 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001009218 | SCV004227285 | pathogenic | not provided | 2022-05-31 | criteria provided, single submitter | clinical testing | PM2, PM3, PS3, PVS1 |
OMIM | RCV000054421 | SCV000082898 | pathogenic | Hereditary spastic paraplegia 26 | 2013-07-11 | no assertion criteria provided | literature only | |
Section for Clinical Neurogenetics, |
RCV000054421 | SCV001156080 | likely pathogenic | Hereditary spastic paraplegia 26 | 2019-08-01 | no assertion criteria provided | research |