ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro) (rs201689565)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414944 SCV000492879 likely pathogenic Gait disturbance; Spastic paraparesis; Difficulty walking; Generalized hyperreflexia 2015-05-05 criteria provided, single submitter clinical testing
Invitae RCV000801301 SCV000941072 uncertain significance Spastic paraplegia 11, autosomal recessive 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1794 of the SPG11 protein (p.Leu1794Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs201689565, ExAC 0.02%). This variant has been observed in combination with another SPG11 variant in an individual affected with hereditary spastic paraplegia (PMID: 26374131). ClinVar contains an entry for this variant (Variation ID: 374112). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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