ClinVar Miner

Submissions for variant NM_002016.2(FLG):c.4162C>T (p.Arg1388Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004785141 SCV005397669 likely pathogenic Ichthyosis vulgaris 2023-11-15 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (C>T) in the last of the 3 exons in the FLG gene that changes Arg1388 to an early termination codon.This variant is expected to truncate the FLG encoded profilaggrin protein thereby disrupting C terminal domain; loss of the C terminal domain prevents processing profilaggrin into filaggrin monomers, generating a loss of function variant (PMID: 17417636, 22071473). This variant is absent from ClinVar and has been observed in individuals affected by atopic dermatitis (PMID: 31365035). This variant is present in 16 of 403388 alleles (0.0040%) in the gnomAD population dataset. Haploinsufficiency in FLG is a known mechanism of disease. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1
GeneDx RCV005241571 SCV005888979 pathogenic not provided 2024-09-16 criteria provided, single submitter clinical testing Reported in individuals with atopic dermatitis (PMID: 31365035); Nonsense variant predicted to result in protein truncation, as the last 2674 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 31365035)

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