Table 1.
Whole exome sequence and comprehensive mitochondrial nuclear gene panel results. Table showing the location of variants found in the proband including cDNA change, protein change, in silico prediction algorithm results, zygosity, mode of inheritance, association with disease, ACMG variant classification, population frequency (ExAC and ESP), rs number, and ClinVar accession number
| Test | Gene | RefSeq Accession Number | cDNA change | Protein Change | SIFT | PolyPhen‐2 | MutationTaster2 | Zygosity | Inheritance | Mode of Inheritance | OMIM | ACMG classification | ExAC Frequency | ESP Frequency | DbSNP | ClinVar Accession |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GeneDx XomeDx/Whole Exome Sequence Analysis | RYR1 | NM_000540.2 | c.7060_7062del | p.Val2354del | N/A | N/A | N/A | Heterozygous | Maternal | AD/AR | Central core disease MIM: 117000; Neuromuscular disease, congenital, with uniform type 1 fiber MIM: 117000; King‐Denborough syndrome MIM: 145600; Minicore myopathy with external ophthalmoplegia MIM: 255320; {Malignant hyperthermia susceptibility 1} MIM: 145600 | Likely Pathogenic Variant | N/R | N/R | N/R | |
| GeneDx XomeDx/Whole Exome Sequence Analysis | RYR1 | NM_000540.2 | c.4485_4500del | p.Tyr1495X | N/A | N/A | N/A | Heterozygous | Paternal | AD/AR | Central core disease MIM: 117000; Neuromuscular disease, congenital, with uniform type 1 fiber MIM: 117000; King‐Denborough syndrome MIM: 145600; Minicore myopathy with external ophthalmoplegia MIM: 255320; {Malignant hyperthermia susceptibility 1} MIM: 145600 | Pathogenic Variant | N/R | N/R | N/R | |
| GeneDx Comprehensive Mitochondrial Nuclear Gene Panel | MT‐CO2 | NC_012920.1 | c.136C>T | p.Leu46Phe | Tolerated | Probably Damaging | N/A | Homoplasmic | N/A | MT | Cytochrome c oxidase deficiency MIM: 220110 N/R | VUS | N/A | N/A | N/R | |
| GeneDx Comprehensive Mitochondrial Nuclear Gene Panel | SARS2 | NM_001145901.1 | c.14T>C | p.Met5Thr | Tolerated | Benign | Polymorphism | Heterozygous | Paternal | AR | Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, HUPRA Syndrome MIM: 613845 | VUS | 0.00000008 | N/R | rs538446780 | N/R |
| GeneDx Comprehensive Mitochondrial Nuclear Gene Panel | AGK | NM_018238.3 | c.416C>G | p.Thr139Arg | Tolerated | Benign | Polymorphism | Heterozygous | Maternal | AR | Autosomal recessive cataract 38 MIM: 614691; Sengers syndrome MIM: 212350 | VUS | 0.00000448 | EA: G = 0.00% – AA: G = 0.43% | rs144706178 | N/R |
| GeneDx Comprehensive Mitochondrial Nuclear Gene Panel | TIMM44 | NM_006351.3 | c.1340G>C | p.Ser447Thr | Tolerated | Benign | Disease causing | Heterozygous | N/A | N/R | N/R | VUS | 0.00001612 | EA: G = 0.00% – AA: G = 1.79% | rs7257461 | N/R |
| GeneDx Comprehensive Mitochondrial Nuclear Gene Panel | PNPT1 | NM_033109.4 | N/A | N/A | N/A | N/A | N/A | Het | N/A | AR | Combined oxidative phosphorylation deficiency 13 MIM: 614932; autosomal recessive deafness 70 MIM: 614934 | VUS | N/R | N/R | N/R |
N/A, not available; N/R, not reported; VUS, variant of uncertain significance.