ClinVar Miner

Submissions for variant NM_003119.4(SPG7):c.1192C>T (p.Arg398Ter)

gnomAD frequency: 0.00002  dbSNP: rs1373388852
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657638 SCV000779383 pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing The R398X nonsense variant in the SPG7 gene has been reported previously in association with spastic paraplegia type 7 when present in the homozygous state or in trans with another disease-causing variant (Pfeffer et al., 2015; Yahikozawa et al., 2015; Schlipf et al., 2011). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R398X variant is observed in 1/7200 (0.006%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). We interpret R398X as a pathogenic variant.
Invitae RCV001855358 SCV002233924 pathogenic Hereditary spastic paraplegia 7 2023-06-28 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: 545964). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 21623769, 25681447). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg398*) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162).
CeGaT Center for Human Genetics Tuebingen RCV000657638 SCV002563366 pathogenic not provided 2020-09-01 criteria provided, single submitter clinical testing
GeneReviews RCV001855358 SCV004034075 not provided Hereditary spastic paraplegia 7 no assertion provided literature only

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