Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001949168 | SCV002211374 | uncertain significance | Hereditary spastic paraplegia 39 | 2024-02-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1248 of the PNPLA6 protein (p.Glu1248Lys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PNPLA6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1439199). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PNPLA6 protein function. 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. |
| Ambry Genetics | RCV004955935 | SCV005474542 | uncertain significance | Inborn genetic diseases | 2024-07-10 | criteria provided, single submitter | clinical testing | The c.3742G>A (p.E1248K) alteration is located in exon 33 (coding exon 31) of the PNPLA6 gene. This alteration results from a G to A substitution at nucleotide position 3742, causing the glutamic acid (E) at amino acid position 1248 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |