Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000499561 | SCV000598185 | pathogenic | Mitochondrial DNA depletion syndrome 13 | 2017-08-10 | criteria provided, single submitter | clinical testing | The NM_012160.4:c.616C>T (NP_036292.2:p.Arg206Ter) [GRCH38: NC_000006.12:g.98917616G>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). 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. 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. |
Fulgent Genetics, |
RCV000499561 | SCV002805606 | likely pathogenic | Mitochondrial DNA depletion syndrome 13 | 2022-03-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV005338208 | SCV006004562 | pathogenic | Inborn genetic diseases | 2025-01-09 | criteria provided, single submitter | clinical testing | The c.616C>T (p.R206*) alteration, located in exon 4 (coding exon 2) of the FBXL4 gene, consists of a C to T substitution at nucleotide position 616. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 206. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.006% (2/31402) total alleles studied. The highest observed frequency was 0.023% (2/8712) of African alleles. This variant has been identified in the homozygous state in multiple individuals with clinical features consistent with FBXL4-related mitochondrial DNA depletion syndrome (El-Hattab, 2017; Trujillano, 2017). Based on the available evidence, this alteration is classified as pathogenic. |