ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.6899T>C (p.Leu2300Pro)

gnomAD frequency: 0.00001  dbSNP: rs371334506
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000224979 SCV000281762 pathogenic Charcot-Marie-Tooth disease axonal type 2X 2016-04-14 criteria provided, single submitter research
GeneDx RCV000498920 SCV000589883 likely pathogenic not provided 2024-10-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27217339, 28554332)
Labcorp Genetics (formerly Invitae), Labcorp RCV000706352 SCV000835396 pathogenic Hereditary spastic paraplegia 11 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2300 of the SPG11 protein (p.Leu2300Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 27217339, 28554332; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 235890). 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 SPG11 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000224979 SCV002763643 likely pathogenic Charcot-Marie-Tooth disease axonal type 2X criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000706352 SCV002763644 likely pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing

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