Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002027641 | SCV002307825 | pathogenic | not provided | 2025-01-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu53Profs*5) in the MDH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MDH2 are known to be pathogenic (PMID: 27989324). This variant is present in population databases (rs782759642, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MDH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1520513). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002548963 | SCV003684861 | pathogenic | Inborn genetic diseases | 2021-06-22 | criteria provided, single submitter | clinical testing | The c.157dupC (p.L53Pfs*5) alteration, located in exon 2 (coding exon 2) of the MDH2 gene, consists of a duplication of C at position 157, causing a translational frameshift with a predicted alternate stop codon after 5 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the MDH2 c.157dupC alteration was observed in 0.009% (25/282,836) of total alleles studied, with a frequency of 0.02% (5/24,964) in the African subpopulation. Based on the available evidence, this alteration is classified as pathogenic. |
Fulgent Genetics, |
RCV005032132 | SCV005667482 | likely pathogenic | Developmental and epileptic encephalopathy, 51 | 2024-05-21 | criteria provided, single submitter | clinical testing |