ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.7802G>A (p.Cys2601Tyr)

dbSNP: rs1060500721
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002230324 SCV000543690 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 2593 of the FLNA protein (p.Cys2593Tyr). 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: 405458). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507907 SCV000603746 uncertain significance not provided 2017-05-05 criteria provided, single submitter clinical testing The p.Cys2593Tyr variant has not been reported in the medical literature or gene specific variation databases but it has been reported to ClinVar (Variation ID: 405458). It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Exome Aggregation Consortium (ExAC) browser. The cysteine at position 2593 is highly conserved, up to Tetraodon (considering 10 species, Alamut v.2.9.0) and computational analyses of the effects of the p.Cys2593Tyr variant on protein structure and function predict a deleterious effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Cys2593Tyr variant with certainty.

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