Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213835 | SCV001385485 | uncertain significance | Dilated Cardiomyopathy, Recessive | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 373 of the PLEKHM2 protein (p.Gln373Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PLEKHM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 943612). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002561827 | SCV003719200 | uncertain significance | Inborn genetic diseases | 2022-07-26 | criteria provided, single submitter | clinical testing | The c.1118A>G (p.Q373R) alteration is located in exon 9 (coding exon 9) of the PLEKHM2 gene. This alteration results from a A to G substitution at nucleotide position 1118, causing the glutamine (Q) at amino acid position 373 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |