ClinVar Miner

Submissions for variant NM_001370298.3(FGD4):c.980T>A (p.Leu327Gln)

gnomAD frequency: 0.00006  dbSNP: rs144980336
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236923 SCV000293026 uncertain significance not provided 2025-01-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000654106 SCV000775996 uncertain significance Charcot-Marie-Tooth disease type 4 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 190 of the FGD4 protein (p.Leu190Gln). This variant is present in population databases (rs144980336, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FGD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 245858). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV002347922 SCV002647491 uncertain significance Inborn genetic diseases 2021-07-14 criteria provided, single submitter clinical testing The p.L190Q variant (also known as c.569T>A), located in coding exon 2 of the FGD4 gene, results from a T to A substitution at nucleotide position 569. The leucine at codon 190 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003600371 SCV004564432 uncertain significance Charcot-Marie-Tooth disease type 4H 2023-02-17 criteria provided, single submitter clinical testing The FGD4 c.569T>A; p.Leu190Gln variant (rs144980336), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245858). This variant is found in the general population with an overall allele frequency of 0.0065% (18/278612 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.100). Due to limited information, the clinical significance of this variant is uncertain at this time.

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