ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1721C>T (p.Pro574Leu)

dbSNP: rs779731686
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Total submissions: 5
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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 RCV000500287 SCV000598506 uncertain significance Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.1721C>T (NP_036292.2:p.Pro574Leu) [GRCH38: NC_000006.12:g.98874423G>A] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Conflicting Evidence based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. BP4:Computational evidence/predictors indicate no impact on the FBXL4 structure, function, or protein-protein interaction. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Conflicting Evidence.
Invitae RCV002524392 SCV002938759 uncertain significance not provided 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 574 of the FBXL4 protein (p.Pro574Leu). This variant is present in population databases (rs779731686, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FBXL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 437799). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBXL4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002524393 SCV003548765 uncertain significance Inborn genetic diseases 2021-08-23 criteria provided, single submitter clinical testing The c.1721C>T (p.P574L) alteration is located in exon 9 (coding exon 7) of the FBXL4 gene. This alteration results from a C to T substitution at nucleotide position 1721, causing the proline (P) at amino acid position 574 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000500287 SCV003834039 uncertain significance Mitochondrial DNA depletion syndrome 13 2022-12-08 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002524392 SCV004223899 uncertain significance not provided 2023-01-11 criteria provided, single submitter clinical testing BP4, PM2

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