ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.7628G>A (p.Cys2543Tyr) (rs201762017)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000435841 SCV000535589 uncertain significance not specified 2017-01-04 criteria provided, single submitter clinical testing The C2535Y variant of uncertain significance in the FLNA gene has not been published as pathogenic or benign variant to our knowledge. This variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or with any significant frequency in the Exome Aggregation Consortium, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved across species, and 2 of 3 in silico algorithms predict C2535Y likely does not alter the protein structure/function.
Invitae RCV000559847 SCV000639837 uncertain significance Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2017-06-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 2535 of the FLNA protein (p.Cys2535Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs201762017, ExAC 0.002%). This variant has not been reported in the literature in individuals with a FLNA-related disease. ClinVar contains an entry for this variant (Variation ID: 392335). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on FLNA function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratoire de Cytogenetique,Hospices Civils de Lyon RCV000760220 SCV000890050 uncertain significance Cardiac valvular dysplasia, X-linked; FG syndrome 2; Periventricular nodular heterotopia 1; Intestinal pseudoobstruction neuronal chronic idiopathic X-linked; Melnick-Needles syndrome; Oto-palato-digital syndrome, type I; Oto-palato-digital syndrome, type II; Terminal osseous dysplasia; Frontometaphyseal dysplasia 2017-12-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762685 SCV000893020 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing

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