ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.1991G>A (p.Arg664His)

gnomAD frequency: 0.00002  dbSNP: rs1271495778
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810134 SCV000950324 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-05-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 664 of the FLNA protein (p.Arg664His). 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: 654219). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function with a negative predictive value of 95%. 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.
Blueprint Genetics RCV001597215 SCV001832421 uncertain significance not provided 2019-11-30 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001597215 SCV004225706 uncertain significance not provided 2022-06-29 criteria provided, single submitter clinical testing PP2, PM2_supporting
GeneDx RCV001597215 SCV005326713 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function

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