ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.2254G>A (p.Val752Ile) (rs1297013254)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497359 SCV000589929 uncertain significance not provided 2017-06-06 criteria provided, single submitter clinical testing The V752I variant in the FLNA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V752I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V752I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V752I as a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000764864 SCV000896020 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 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001057064 SCV001221539 uncertain significance Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2019-12-20 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 752 of the FLNA protein (p.Val752Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with generalized epilepsy (PMID: 30986657). ClinVar contains an entry for this variant (Variation ID: 432226). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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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