ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.3775C>T (p.Gln1259Ter)

dbSNP: rs1557177663
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497491 SCV000590138 pathogenic not provided 2017-06-06 criteria provided, single submitter clinical testing The Q1259X nonsense variant in the FLNA gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q1259X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Labcorp Genetics (formerly Invitae), Labcorp RCV003766799 SCV004603911 pathogenic Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-02-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1259*) in the FLNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNA are known to be pathogenic (PMID: 16684786, 20730588, 26471271). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 432416). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004767308 SCV005381411 pathogenic Periventricular nodular heterotopia 2024-08-05 criteria provided, single submitter clinical testing Variant summary: FLNA c.3775C>T (p.Gln1259X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 179786 control chromosomes. To our knowledge, no occurrence of c.3775C>T in individuals affected with Periventricular Nodular Heterotopia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 432416). Based on the evidence outlined above, the variant was classified as pathogenic.

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