ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.7255C>T (p.Arg2419Ter) (rs782308324)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000215801 SCV000279727 pathogenic not provided 2016-01-08 criteria provided, single submitter clinical testing The R2411X pathogenic variant in the FLNA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R2411X variant was not observed in approximately 6200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Protein truncating pathogenic variants downstream of this variant have been reported in the Human Gene Mutation Database in association with FLNA-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. We interpret R2411X as a pathogenic variant
Invitae RCV001224993 SCV001397228 pathogenic Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2019-04-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2411*) in the FLNA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with periventricular nodular heterotopia (PMID: 26471271). This variant is also known as c.7255C>T (p.Arg2419*) in the literature. ClinVar contains an entry for this variant (Variation ID: 234717). Loss-of-function variants in FLNA are known to be pathogenic (PMID: 16684786, 20730588, 26471271). For these reasons, this variant has been classified as Pathogenic.

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