ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1056A>T (p.Leu352Phe)

dbSNP: rs779748858
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Total submissions: 3
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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 RCV000504145 SCV000598382 uncertain significance Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.1056A>T (NP_036292.2:p.Leu352Phe) [GRCH38: NC_000006.12:g.98905473T>A] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Insufficient 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. PP3:Computational evidence/predictors indicate the variant has deleterious effect on FBXL4 structure, function, or protein-protein interaction. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Insufficient Evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV001347302 SCV001541554 uncertain significance not provided 2022-07-25 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 437678). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 352 of the FBXL4 protein (p.Leu352Phe). This variant is present in population databases (rs779748858, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FBXL4-related conditions. 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 RCV002527322 SCV003574544 uncertain significance Inborn genetic diseases 2021-08-12 criteria provided, single submitter clinical testing The c.1056A>T (p.L352F) alteration is located in exon 5 (coding exon 3) of the FBXL4 gene. This alteration results from a A to T substitution at nucleotide position 1056, causing the leucine (L) at amino acid position 352 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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