ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.704_705del (p.His235fs)

gnomAD frequency: 0.00002  dbSNP: rs312262719
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000034260 SCV000290932 pathogenic Hereditary spastic paraplegia 11 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His235Argfs*12) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is present in population databases (rs312262719, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia and Charcot-Marie-Tooth disease (PMID: 18079167, 22696581, 26556829). ClinVar contains an entry for this variant (Variation ID: 41359). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000599551 SCV000709972 pathogenic not provided 2020-05-13 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18079167, 29946510, 22154821, 19224311, 31589614)
Paris Brain Institute, Inserm - ICM RCV000034260 SCV001451239 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000034260 SCV002762878 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000034260 SCV004045859 pathogenic Hereditary spastic paraplegia 11 2023-07-14 criteria provided, single submitter clinical testing
GeneReviews RCV000034260 SCV000058200 not provided Hereditary spastic paraplegia 11 no assertion provided literature only

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