Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826110 | SCV000967618 | likely pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2018-12-12 | criteria provided, single submitter | clinical testing | The p.Ala19ProfsX3 variant in GFM1 has not been previously reported in individua ls with combined oxidative phosphorylation deficiency. It has been identified in 1/80660 of European and 1/24940 South Asian chromosomes by gnomAD (http://gnoma d.broadinstitute.org). This variant is predicted to cause a frameshift, which al ters the protein?s amino acid sequence beginning at position 19 and leads to a p remature termination codon 3 amino acids downstream. This alteration is then pre dicted to lead to a truncated or absent protein. Loss of function of the GFM1 ge ne is associated with autosomal recessive combined oxidative phosphorylation def iciency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as like ly pathogenic for autosomal recessive combined oxidative phosphorylation deficie ncy. ACMG/AMP Criteria applied: PVS1_Strong, PM2. |
| Labcorp Genetics |
RCV002538243 | SCV003326122 | pathogenic | not provided | 2022-03-16 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 667375). This variant has not been reported in the literature in individuals affected with GFM1-related conditions. This sequence change creates a premature translational stop signal (p.Ala19Profs*3) 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). |
| Baylor Genetics | RCV000826110 | SCV005058974 | likely pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2023-12-23 | criteria provided, single submitter | clinical testing |