Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779273 | SCV000915850 | uncertain significance | Hereditary spastic paraplegia 39 | 2018-10-10 | criteria provided, single submitter | clinical testing | The PNPLA6 c.3598C>G (p.Gln1200Glu) variant is a missense variant has been reported in one study and is found in one individual in a compound heterozygous state (Fogel et al. 2014). This male individual was 58 years old and presented with upper motor neuron features, spasticity, and an inheritance that was sporadic. Control data are unavailable for this variant, which it is reported at a frequency of 0.000619 in the Other population of the Genome Aggregation Database. Based on the limited evidence, the p.Gln1200Glu variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive spastic paraplegia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV000779273 | SCV001221675 | uncertain significance | Hereditary spastic paraplegia 39 | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1200 of the PNPLA6 protein (p.Gln1200Glu). This variant is present in population databases (rs143072391, gnomAD 0.03%). This missense change has been observed in individual(s) with chronic progressive cerebellar ataxia (PMID: 25133958). ClinVar contains an entry for this variant (Variation ID: 632325). 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 tolerated. 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 |
RCV002245664 | SCV002513160 | uncertain significance | not provided | 2023-11-28 | criteria provided, single submitter | clinical testing | Identified along with a second PNPL6 variant in a patient with ataxia, but familial segregation information was not included and evidence in support of pathogenicity for the variant was not provided (PMID: 25133958); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25631098, 25480986, 25133958) |
| Ambry Genetics | RCV002536857 | SCV003645046 | uncertain significance | Inborn genetic diseases | 2022-03-02 | criteria provided, single submitter | clinical testing | The c.3598C>G (p.Q1200E) alteration is located in exon 32 (coding exon 30) of the PNPLA6 gene. This alteration results from a C to G substitution at nucleotide position 3598, causing the glutamine (Q) at amino acid position 1200 to be replaced by a glutamic acid (E). Based on data from gnomAD, the G allele has an overall frequency of 0.02% (47/282758) total alleles studied. This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |