ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.233T>A (p.Leu78Ter) (rs121918358)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neurogenetics of motion laboratory,Montreal Neurological Institute RCV000007218 SCV000245724 pathogenic Spastic paraplegia 7 criteria provided, single submitter case-control
GeneDx RCV000200640 SCV000252327 pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing The apparently maternally L78X pathogenic variant in the SPG7 gene was reported previously in the homozygous state in affected individuals in two spastic paraplegia families (Arnoldi et al., 2008). Another study reported L78X in the homozygous state in some affected individuals in a spastic paraplegia family, but also in the heterozygous state in one of the affected individuals, suggesting possible autosomal dominant inheritance in that family (Sanchez-Ferrero et al., 2013). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The L78X variant was observed in 0.01% (1/8600) alleles from individuals of European American ancestryand 0% (0/4396) alleles from individuals of African American ancestry in the NHLBI Exome Sequencing Project. We interpret L78X as a pathogenic variant.
Invitae RCV000007218 SCV000640076 pathogenic Spastic paraplegia 7 2018-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 78 (p.Leu78*). It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs121918358, ExAC 0.3%). This particular variant has been observed in the literature in the homozygous state in 5 individuals from 3 families affected with HSP (PMID: 18200586, 22571692). It has also been reported in the heterozygous state in affected individuals in the absence of a second pathogenic variant (PMID: 22571692, 24727571). However, given the frequency of this variant in the general population, it is unlikely that it acts as a dominant allele. ClinVar contains an entry for this variant (Variation ID: 6816). Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000200640 SCV000844104 pathogenic not provided 2017-12-22 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000007218 SCV000930176 uncertain significance Spastic paraplegia 7 2019-04-27 criteria provided, single submitter clinical testing
OMIM RCV000007218 SCV000027414 pathogenic Spastic paraplegia 7 2008-04-01 no assertion criteria provided literature only
Institute of Human Genetics,Cologne University RCV000664258 SCV000787827 uncertain significance Proximal spinal muscular atrophy 2018-04-26 no assertion criteria provided clinical testing

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