Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Wong Mito Lab, |
RCV000504121 | SCV000598193 | pathogenic | Mitochondrial DNA depletion syndrome 13 | 2017-08-10 | criteria provided, single submitter | clinical testing | The NM_012160.4:c.1067del (NP_036292.2:p.Gly356AlafsTer15) [GRCH38: NC_000006.12:g.98905463del] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:23993194 ; 25868664 . This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predcted null variant in FBXL4 where loss of function is a known mechanism of disease. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 13 which is a recessive disorder. PP4:Patient’s phenotype or family history is highly specific for FBXL4. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic. |
| Gene |
RCV000657172 | SCV000778893 | pathogenic | not provided | 2018-05-21 | criteria provided, single submitter | clinical testing | The c.1067delG variant has been reported previously in the homozygous and compound heterozygous states in patients with symptoms that include early-onset lactic acidemia, hypotonia, encephalopathy, developmental delay, failure to thrive, microcephaly and defects in the respiratory chain (Gai et al. 2013; Huemer et al. 2015; Al-Shamsi et al. 2016). The c.1067delG variant is not observed in large population cohorts (Lek et al., 2016). The c.1067delG variant causes a frameshift starting with codon Glycine 356, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Gly356AlafsX15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic. |
| Baylor Genetics | RCV000504121 | SCV000807421 | pathogenic | Mitochondrial DNA depletion syndrome 13 | 2017-09-01 | criteria provided, single submitter | clinical testing | This mutation has been previously reported as disease-causing and was found twice in our laboratory: once in trans with another pathogenic variant in an 8-year-old female with primary mitochondrial respiratory chain disease; once homozygous in a 3-year-old male with regression, severe failure to thrive, hypotonia, microcephaly, severe lactic acidosis, nystagmus, mild dysmorphisms, and 3 siblings who died in infancy |
| Mayo Clinic Laboratories, |
RCV000657172 | SCV000802753 | likely pathogenic | not provided | 2016-03-08 | no assertion criteria provided | clinical testing |