ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4474+3G>T

gnomAD frequency: 0.00001  dbSNP: rs1286863443
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000597006 SCV000703756 uncertain significance not provided 2016-12-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001867937 SCV002210492 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-01-11 criteria provided, single submitter clinical testing This sequence change falls in intron 26 of the FLNA gene. It does not directly change the encoded amino acid sequence of the FLNA protein. It affects a nucleotide within the consensus splice site. 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: 498636). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224342 SCV003919974 uncertain significance Cardiac valvular dysplasia, X-linked; FG syndrome 2; Heterotopia, periventricular, X-linked dominant; Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked; Melnick-Needles syndrome; Oto-palato-digital syndrome, type I; Oto-palato-digital syndrome, type II; Terminal osseous dysplasia-pigmentary defects syndrome; Frontometaphyseal dysplasia 1 2023-01-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature. It is present in a single heterozygote in gnomAD (Highest reported MAF: 0.002 [1/53247]; https://gnomad.broadinstitute.org/variant/X-154358981-C-A?dataset=gnomad_r3). It is also present in ClinVar (Variation ID: 498636). Splice prediction tools weakly suggest that this variant may affect splicing; however, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV000597006 SCV003936252 uncertain significance not provided 2022-12-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701683 SCV005205140 uncertain significance not specified 2024-06-17 criteria provided, single submitter clinical testing

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