Submissions for variant NM_001110556.2(FLNA):c.6268G>C (p.Val2090Leu)

gnomAD frequency: 0.00001  dbSNP: rs968230475

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002231782	SCV000639818	likely benign	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2023-12-02	criteria provided, single submitter	clinical testing
GeneDx	RCV003332193	SCV004040219	uncertain significance	not provided	2023-03-31	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004787885	SCV005398709	uncertain significance	Heterotopia, periventricular, X-linked dominant	2020-05-21	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VOUS. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene (Cannaerts, E. et al. (2018)). (N) 0109 - This gene is known to be associated with X-linked recessive disease. (N) 0110 - This gene is known to be associated with X-linked dominant disease. (N) 0112 - Variants in this gene are known to have reduced penetrance (Cannaerts, E. et al. (2018)). (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to leucine (exon 39). (N) 0253 - Variant is hemizygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (3 heterozygotes, 0 homozygote, 0 hemizygote). (P) 0502 - Missense variant with conflicting in-silico predictions and/or uninformative conservation (MutationAssessor, FATHMM, PolyPhen2, PROVEAN, UCSC). (N) 0600 - Variant is located in an annotated domain or motif (Filamin/ABP280 repeat domain; PDB) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000656208	SCV000678402	uncertain significance	Wolff-Parkinson-White pattern	2017-07-14	no assertion criteria provided	research	This variant was identified in an individual with Wolff-Parkinson-White syndrome