ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.689C>G (p.Thr230Arg)

dbSNP: rs1556270495
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543384 SCV000639462 uncertain significance Hereditary spastic paraplegia 2 2017-12-01 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 230 of the PLP1 protein (p.Thr230Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PLP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. A different missense substitution at this codon (p.Thr230Ile) has been reported in an affected individual, but the clinical significance of this observation is not known (PMID: 21679407). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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