ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.125A>G (p.Lys42Arg)

dbSNP: rs1569551930
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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 RCV002233290 SCV000823998 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2018-03-17 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 42 of the FLNA protein (p.Lys42Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). 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 C0"). 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 RCV002424658 SCV002681046 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2017-12-15 criteria provided, single submitter clinical testing The p.K42R variant (also known as c.125A>G), located in coding exon 1 of the FLNA gene, results from an A to G substitution at nucleotide position 125. The lysine at codon 42 is replaced by arginine, an amino acid with highly similar properties. This alteration has been detected in a female with grey matter heterotopia at our laboratory, and reported to segregate with hypoplastic left heart syndrome in her two sons. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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