Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001207728 | SCV001379093 | pathogenic | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg47*) in the GFM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GFM1 are known to be pathogenic (PMID: 16632485, 17160893). This variant is present in population databases (rs119470019, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with GFM1-related conditions (PMID: 17160893). ClinVar contains an entry for this variant (Variation ID: 4161). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004378 | SCV004121768 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2023-10-17 | criteria provided, single submitter | clinical testing | Variant summary: GFM1 c.139C>T (p.Arg47X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 251442 control chromosomes. c.139C>T has been reported in the literature in at least one compound heterozygous individual affected with early-onset Leigh syndrome with evidence of familial co-segregation (e.g.Valente_2007). One publication reports experimental evidence evaluating an impact on protein function, however, does not provide sufficient evidence about the variant effect (e.g.Valente_2007). The following publication has been ascertained in the context of this evaluation (PMID: 17160893). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000004378 | SCV004199321 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2023-07-14 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004378 | SCV000024550 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2007-01-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000004378 | SCV002081585 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2020-03-02 | no assertion criteria provided | clinical testing |