Total submissions: 7
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, |
RCV001420581 | SCV002765164 | pathogenic | Parkinsonism-dystonia, infantile, 2 | 2022-12-21 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001420581 | SCV003823331 | uncertain significance | Parkinsonism-dystonia, infantile, 2 | 2021-08-19 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
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. |
Applied Translational Genetics Group, |
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 |