ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1303C>T (p.Arg435Ter) (rs201889294)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000056328 SCV000598187 pathogenic Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) 2017-08-10 criteria provided, single submitter clinical testing The NM_012160.4:c.1303C>T (NP_036292.2:p.Arg435Ter) [GRCH38: NC_000006.12:g.98899282G>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:23993193 ; 27099744 . 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. PP5:Reputable source(s) suggest that the variant is pathogenic. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000604628 SCV000731341 pathogenic Mitochondrial DNA depletion syndrome 2016-12-23 criteria provided, single submitter clinical testing The p.Arg435X (NM_012160.4 c.1303C>T) variant in FBXL4 has been reported in 1 ho mozygous and 2 compound heterozygous individuals with clinical features of mitoc hondrial DNA depletion syndrome 13 (Bonnen 2013, Van Rij 2016, and Prionska 2016 ). This variant has been identified in 0.012% (1/8652) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC,; dbSN P rs201889294). This nonsense variant leads to a premature termination codon at position 435, which is predicted to lead to a truncated or absent protein. In su mmary, the p.Arg435X variant meets criteria to be classified as pathogenic for m itochondrial DNA depletion syndrome in an autosomal recessive manner, based upon occurrence in patients and predicted functional impact.
Ambry Genetics RCV000622490 SCV000740716 pathogenic Inborn genetic diseases 2014-08-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
OMIM RCV000056328 SCV000087497 pathogenic Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) 2013-09-05 no assertion criteria provided literature only

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