ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.4726G>A (p.Gly1576Arg) (rs797045044)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000191086 SCV000245482 likely pathogenic Cardiac valvular dysplasia, X-linked 2013-10-15 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our laboratory maternally inherited in a 34-year-old male with aortic stenosis, mitral valve stenosis, reduced joint range of motion, and spontaneous keloids. A maternal male second cousin with similar features was also hemizygous for the variant.
Invitae RCV000794294 SCV000933692 pathogenic Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2019-06-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1576 of the FLNA protein (p.Gly1576Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with X-linked FLNA related syndrome in families (PMID: 26686323, 26804200). ClinVar contains an entry for this variant (Variation ID: 209154). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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