ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.2179G>A (p.Gly727Ser)

gnomAD frequency: 0.00002  dbSNP: rs1460177575
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001900906 SCV002163705 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 727 of the FLNA protein (p.Gly727Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with FLNA-related conditions (PMID: 31069529, 32738303, 33448881). ClinVar contains an entry for this variant (Variation ID: 1394429). 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. 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.
Ambry Genetics RCV002425189 SCV002726717 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-05-14 criteria provided, single submitter clinical testing The p.G727S variant (also known as c.2179G>A), located in coding exon 14 of the FLNA gene, results from a G to A substitution at nucleotide position 2179. The glycine at codon 727 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004728911 SCV005332407 uncertain significance not provided 2023-06-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33448881, 32738303, 31069529)

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