ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.737G>C (p.Gly246Ala)

dbSNP: rs398123467
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079102 SCV000110971 pathogenic not provided 2013-01-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000794114 SCV000933503 likely pathogenic Hereditary spastic paraplegia 2 2018-10-24 criteria provided, single submitter clinical testing This variant disrupts the p.Gly246 amino acid residue in PLP1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10417279, 24139698), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change results in the rapid degradation of the PLP1 protein (PMID: 19825935). This variant has been observed in an individual affected with Pelizaeus-Merzbacher disease (PMID: 15712223). This variant is also known as G245A in the literature. ClinVar contains an entry for this variant (Variation ID: 93235). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 246 of the PLP1 protein (p.Gly246Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV004595494 SCV005088501 likely pathogenic Pelizaeus-Merzbacher disease 2022-01-31 criteria provided, single submitter clinical testing This missense variant (c.737G>C, p.Gly246Ala) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 15712223, PMID 19825935). Variant prediction programs support a deleterious effect on the protein, but functional studies have not been reported.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.