ClinVar Miner

Submissions for variant NM_002016.2(FLG):c.6109C>T (p.Arg2037Ter)

gnomAD frequency: 0.00054  dbSNP: rs200002200
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000261767 SCV000330061 pathogenic not provided 2023-12-18 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 2025 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); This variant is associated with the following publications: (PMID: 33807935, 31967959, 37067103, 37995928, 36751330, 16444271)
Mendelics RCV002248503 SCV002516386 pathogenic Ichthyosis vulgaris 2022-05-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000261767 SCV002821419 pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing FLG: PVS1, PP1, PP4
Genome-Nilou Lab RCV002248503 SCV004050233 pathogenic Ichthyosis vulgaris 2023-04-11 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000261767 SCV004243260 pathogenic not provided 2025-03-04 criteria provided, single submitter clinical testing
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV002248503 SCV005397770 pathogenic Ichthyosis vulgaris 2024-06-17 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (G>A) at position 6109 of the coding sequence of the FLG gene that results in an arginine to an early termination codon at residue 2037 of the filaggrin protein. This variant is in the C-terminus of FLG and is predicted to generate a non-functional allele through the expression of a truncated protein. This is a previously reported variant (ClinVar 280166) that has been observed in individuals affected by congenital ichthyosis and/or atopic dermatitis, with variable penetrance and expressivity (PMID: 33807935, 37067103, 36751330). This variant is present in the gnomAD v4.1.0 population database (304 in 1614090 alleles, 0.018%). Loss of function is disease causing in this gene (PMID: 16444271). Given this evidence, we consider this variant to be pathogenic. ACMG Criteria: PP1, PP5, PVS1
Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare RCV002248503 SCV005873743 likely pathogenic Ichthyosis vulgaris 2021-05-06 criteria provided, single submitter clinical testing

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