ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1507C>T (p.Arg503Trp) (rs864622162)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204046 SCV000259516 pathogenic Spastic paraplegia 4, autosomal dominant 2019-02-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 503 of the SPAST protein (p.Arg503Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hereditary spastic paraplegia (PMID: 16055926, 18701882, 17594340, 20932283). ClinVar contains an entry for this variant (Variation ID: 219575). 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. The observation of one or more missense substitutions at this codon (p.Arg503Leu and p.Arg503Pro) in affected individuals suggests that this may be a clinically significant residue (PMID: 12552568, 26374131). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585136 SCV000692984 likely pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Codex Genetics Limited RCV000204046 SCV000996004 pathogenic Spastic paraplegia 4, autosomal dominant 2019-02-28 no assertion criteria provided provider interpretation

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