Submissions for variant NM_001457.4(FLNB):c.1196A>G (p.Lys399Arg)

gnomAD frequency: 0.00043  dbSNP: rs145673747

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000658964	SCV000618210	likely benign	not provided	2020-04-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658964	SCV000780767	uncertain significance	not provided	2017-12-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000487	SCV001157370	likely benign	not specified	2019-02-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001150046	SCV001311053	uncertain significance	FLNB-Related Spectrum Disorders	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000658964	SCV001672483	likely benign	not provided	2024-01-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002279314	SCV002566642	uncertain significance	Connective tissue disorder	2019-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525132	SCV003686323	uncertain significance	Inborn genetic diseases	2021-01-07	criteria provided, single submitter	clinical testing	The c.1196A>G (p.K399R) alteration is located in exon 8 (coding exon 8) of the FLNB gene. This alteration results from a A to G substitution at nucleotide position 1196, causing the lysine (K) at amino acid position 399 to be replaced by an arginine (R). The p.K399R alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003419907	SCV004106460	uncertain significance	FLNB-related condition	2023-05-11	criteria provided, single submitter	clinical testing	The FLNB c.1196A>G variant is predicted to result in the amino acid substitution p.Lys399Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.074% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-58084486-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.