ClinVar Miner

Submissions for variant NM_144599.5(NIPA1):c.134C>G (p.Thr45Arg)

dbSNP: rs104894496
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000002628 SCV001406668 pathogenic Hereditary spastic paraplegia 6 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 45 of the NIPA1 protein (p.Thr45Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 14508710). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2520). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects NIPA1 function (PMID: 17166836, 19091982, 20816793). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004719611 SCV005325109 pathogenic not provided 2023-10-13 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect and show that this variant affects normal protein function and has profound effects on cellular distributions (Goytain et al., 2007; Botzolakis et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18191948, 19091982, 35181192, 35464835, 19620182, 22302102, 32384786, 22552817, 20816793, 17166836, 14508710)
OMIM RCV000002628 SCV000022786 pathogenic Hereditary spastic paraplegia 6 2003-10-01 no assertion criteria provided literature only

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.