ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.3596C>T (p.Ser1199Leu) (rs28935473)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000012525 SCV000222837 pathogenic Melnick-Needles syndrome 2008-12-17 criteria provided, single submitter clinical testing
Invitae RCV000472168 SCV000543692 pathogenic Oto-palato-digital syndrome, type II 2016-12-23 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 1199 of the FLNA protein (p.Ser1199Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in more than 6 individuals affected with Melnick Needles syndrome, with several of them being reported as de novo events (PMID: 12612583, 20186808, 26404489). ClinVar contains an entry for this variant (Variation ID: 11759). 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 C65"). In summary, this variant is a well established pathogenic rare missense change that has been reported in multiple affected individuals. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012525 SCV000032759 pathogenic Melnick-Needles syndrome 2003-04-01 no assertion criteria provided literature only
GeneReviews RCV000012525 SCV000040827 pathologic Melnick-Needles syndrome 2008-07-25 no assertion criteria provided curation Converted during submission to Pathogenic.

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