ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.620C>T (p.Pro207Leu) (rs28935469)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415125 SCV000492768 pathogenic Short stature; Conductive hearing impairment; Cleft palate 2015-10-21 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000012521 SCV001150103 pathogenic Oto-palato-digital syndrome, type I 2020-01-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000894 SCV001157976 pathogenic not specified 2018-11-20 criteria provided, single submitter clinical testing The FLNA c.620C>T; p.Pro207Leu variant (rs28935469) has been described in individuals with otopalatodigital (OPD) syndrome type I (OPD1), and has shown to segregate with disease in males in at least 2 families (Robertson 2003). It contains an entry in ClinVar (Variation ID: 11755) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 207 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. This variant is located in a calponin homology domain portion of the actin-binding domain, and several variants within this region are associated with OPD syndrome type I and type II, indicating that this domain is likely important for protein function (Hidalgo-Bravo 2005, Kondoh 2007, Marino-Enriquez 2007, Robertson 2003, Sankararaman 2013). Based on available information, this variant is considered pathogenic. REFERENCES Hidalgo-Bravo A et al. A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1 syndrome and extremely skewed X chromosome inactivation. Am J Med Genet A. 2005 Jul 15;136(2):190-3. Kondoh T et al. A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype-genotype correlation. J Hum Genet. 2007;52(4):370-3. Marino-Enriquez A et al. Otopalatodigital syndrome type 2 in two siblings with a novel filamin A 629G>T mutation: clinical, pathological, and molecular findings. Am J Med Genet A. 2007 May 15;143A(10):1120-5. Robertson S et al. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003 Apr;33(4):487-91. Sankararaman S et al. Otopalatodigital syndrome type 2 in a male infant: A case report with a novel sequence variation. J Pediatr Genet. 2013 Mar;2(1):33-6.
OMIM RCV000012521 SCV000032755 pathogenic Oto-palato-digital syndrome, type I 2003-04-01 no assertion criteria provided literature only

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