ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4525G>A (p.Val1509Ile)

dbSNP: rs782018054
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University Hospital Muenster RCV004584440 SCV002562230 uncertain significance See cases 2022-07-18 criteria provided, single submitter clinical testing ACMG categories: PM2,PP3
Ambry Genetics RCV003382628 SCV004096661 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-07-22 criteria provided, single submitter clinical testing The p.V1509I variant (also known as c.4525G>A), located in coding exon 26 of the FLNA gene, results from a G to A substitution at nucleotide position 4525. The valine at codon 1509 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003771765 SCV004570209 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1509 of the FLNA protein (p.Val1509Ile). 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: 1210296). 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.
Institute of Human Genetics, University of Goettingen RCV001580385 SCV001810060 uncertain significance Cardiac valvular dysplasia, X-linked 2021-08-27 no assertion criteria provided clinical testing

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