ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.3368C>G (p.Ser1123Cys)

gnomAD frequency: 0.00003  dbSNP: rs782361719
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002313375 SCV000739124 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-10-24 criteria provided, single submitter clinical testing The p.S1123C variant (also known as c.3368C>G), located in coding exon 21 of the FLNA gene, results from a C to G substitution at nucleotide position 3368. The serine at codon 1123 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002453 SCV001160395 uncertain significance not specified 2019-04-02 criteria provided, single submitter clinical testing The FLNA c.3368C>G; p.Ser1123Cys variant (rs782361719), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 519896). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 1123 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of this variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002531826 SCV003457617 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1123 of the FLNA protein (p.Ser1123Cys). 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: 519896). 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.

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