ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4825G>A (p.Val1609Met)

gnomAD frequency: 0.00001  dbSNP: rs782314291
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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 RCV002232991 SCV000835219 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2018-05-10 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1609 of the FLNA protein (p.Val1609Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with FLNA-related disease. 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV002316005 SCV000849340 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-04-14 criteria provided, single submitter clinical testing The p.V1609M variant (also known as c.4825G>A), located in coding exon 28 of the FLNA gene, results from a G to A substitution at nucleotide position 4825. The valine at codon 1609 is replaced by methionine, an amino acid with highly similar 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.
PreventionGenetics, part of Exact Sciences RCV004735760 SCV005362394 uncertain significance FLNA-related disorder 2024-08-30 no assertion criteria provided clinical testing The FLNA c.4825G>A variant is predicted to result in the amino acid substitution p.Val1609Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0037% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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