ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.560T>C (p.Ile187Thr)

dbSNP: rs132630288
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000011834 SCV003445181 pathogenic Hereditary spastic paraplegia 2 2022-09-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PLP1 function (PMID: 23344956). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 187 of the PLP1 protein (p.Ile187Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with PLP1-related conditions (PMID: 7522741, 19955111, 24139698). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11085). 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 not expected to disrupt PLP1 protein function.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV004595482 SCV005088477 likely pathogenic Pelizaeus-Merzbacher disease 2021-12-15 criteria provided, single submitter clinical testing This missense variant (c.560T>C, p.Ile187Thr) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 31110947, PMID 28286750, PMID 24575297, PMID 23344956, PMId 9427151, PMID 14745569). Variant prediction programs support a deleterious effect on the protein, although no functional studies have been published. The variant has been observed in affected male siblings and is carried by their mother.
OMIM RCV000011834 SCV000032067 pathogenic Hereditary spastic paraplegia 2 2004-04-01 no assertion criteria provided literature only

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