Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000344706 | SCV000451646 | uncertain significance | Parkinson Disease, Dominant | 2016-07-24 | criteria provided, single submitter | clinical testing | The SNCA c.150T>G (His50Gln) missense variant has been reported in a heterozygous state in two individuals with Parkinson disease (Appel-Cresswell et al. 2013; Proukakis et al. 2014). Both individuals appeared to share a common haplotype, suggesting a possible founder effect. The p.His50Gln variant was absent from 1325 controls and is reported at a frequency of 0.00003 in the Total population of the Exome Aggregation Consortium. Functional studies demonstrated that the p.His50Gln variant did not significantly alter the structure of the protein but accelerated SNCA fibril aggregation and oligomerization (Ghosh et al. 2013; Khalaf et al. 2014). The variant was also shown to increase SNCA secretion, extracellular toxicity, and cell death (Khalaf et al. 2014; Petrucci et al. 2015). Based on the collective evidence, the p.His50Gln variant is classified as a variant of unknown significance but suspicious for pathogenicity for Parkinson disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV001301465 | SCV001490635 | uncertain significance | Lewy body dementia; Autosomal dominant Parkinson disease 1 | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 50 of the SNCA protein (p.His50Gln). This variant is present in population databases (rs201106962, gnomAD 0.01%). This missense change has been observed in individual(s) with Parkinson's disease (PMID: 23427326, 23457019, 29398121). ClinVar contains an entry for this variant (Variation ID: 162095). 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 tolerated. Experimental studies have shown that this missense change affects SNCA function (PMID: 23427326, 30528390). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV002307408 | SCV002601357 | uncertain significance | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect leading to accelerated protein aggregation (Ghosh et al., 2013; Porcari et al., 2015; Rutherford et al., 2014); Reported in patients with dopa-responsive Parkinson disease in published literature (Appel-Cresswell et al., 2013; Proukakis et al., 2013); Reported as a somatic variant in brain tissue of an individual with sporadic late-onset Parkinson disease (Proukakis et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26306801, 31980526, 29398121, 23669636, 26076669, 25330418, 26341711, 25554495, 24728187, 25505181, 24984882, 24936070, 25393002, 27573854, 30528390, 31996268, 23916651, 27250986, 23674458, 28650719, 24047453, 23674490, 23427326, 24315198, 23457019, 36099961) |
Fulgent Genetics, |
RCV002498683 | SCV002782207 | uncertain significance | Lewy body dementia; Autosomal dominant Parkinson disease 1; Autosomal dominant Parkinson disease 4 | 2021-12-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV002307408 | SCV004152975 | uncertain significance | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | SNCA: PS3:Supporting |
Mayo Clinic Laboratories, |
RCV002307408 | SCV005410564 | uncertain significance | not provided | 2023-09-27 | criteria provided, single submitter | clinical testing | BS2, PS3, PS4_moderate |
OMIM | RCV000149507 | SCV000196158 | pathogenic | Autosomal dominant Parkinson disease 1 | 2014-08-08 | no assertion criteria provided | literature only |