ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4438G>A (p.Val1480Met)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002293711 SCV002586606 uncertain significance not provided 2022-10-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004047628 SCV003962688 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-04-21 criteria provided, single submitter clinical testing The c.4438G>A (p.V1480M) alteration is located in exon 26 (coding exon 25) of the FLNA gene. This alteration results from a G to A substitution at nucleotide position 4438, causing the valine (V) at amino acid position 1480 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003774980 SCV004576001 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2022-11-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1480 of the FLNA protein (p.Val1480Met). This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 1711993). This variant has not been reported in the literature in individuals affected with FLNA-related conditions.

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