ClinVar Miner

Submissions for variant NM_003054.6(SLC18A2):c.710C>A (p.Pro237His)

dbSNP: rs767337086
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001420581 SCV001622896 uncertain significance Parkinsonism-dystonia, infantile, 2 2020-07-03 criteria provided, single submitter clinical testing
Pediatric/Medical Genetics, Ministry of Health, Qatif Central Hospital RCV001420581 SCV002765164 pathogenic Parkinsonism-dystonia, infantile, 2 2022-12-21 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001420581 SCV003823331 uncertain significance Parkinsonism-dystonia, infantile, 2 2021-08-19 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV001420581 SCV004100610 uncertain significance Parkinsonism-dystonia, infantile, 2 criteria provided, single submitter clinical testing The missense variant p.P237H in SLC18A2 (NM_003054.6) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has been submitted to ClinVar as Uncertain signifcance but no details are avialable for an independent assessment. The p.P237H variant is observed in 4/1,13,688 (0.0035%) alleles from individuals of European (Non-Finnish) background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.P237H missense variant is predicted to be damaging by both SIFT and PolyPhen2. The nucleotide c.710 in SLC18A2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Invitae RCV003558600 SCV004295730 likely pathogenic not provided 2022-12-12 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 666409). This missense change has been observed in individuals with brain dopamine-serotonin vesicular transport disease (PMID: 26497564, 28716265, 34078222). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs767337086, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 237 of the SLC18A2 protein (p.Pro237His). 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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV001420581 SCV004807365 uncertain significance Parkinsonism-dystonia, infantile, 2 2024-03-26 criteria provided, single submitter clinical testing
Applied Translational Genetics Group, University of Auckland RCV000824911 SCV000238543 likely pathogenic Brain dopamine-serotonin vesicular transport disease 2015-06-26 no assertion criteria provided research Homozygous recessive inheritance of a variant causing substitution of an evolutionary conserved amino acid; variant present in a heterozygous state in a single ExAC sample but not reported elsewhere
OMIM RCV001420581 SCV004175903 pathogenic Parkinsonism-dystonia, infantile, 2 2023-12-12 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.