Submissions for variant NM_001457.4(FLNB):c.4391G>C (p.Gly1464Ala)

dbSNP: rs886044175

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000309759	SCV000343789	uncertain significance	not provided	2016-08-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764513	SCV000895595	uncertain significance	Atelosteogenesis type III; Atelosteogenesis type I; Boomerang dysplasia; Spondylocarpotarsal synostosis syndrome; Larsen syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001150331	SCV001311391	uncertain significance	FLNB-Related Spectrum Disorders	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000309759	SCV002310647	uncertain significance	not provided	2022-08-19	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 289425). This variant has not been reported in the literature in individuals affected with FLNB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1464 of the FLNB protein (p.Gly1464Ala).
CeGaT Center for Human Genetics Tuebingen	RCV000309759	SCV005075286	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	FLNB: PM2
Breakthrough Genomics, Breakthrough Genomics	RCV000309759	SCV005189647	uncertain significance	not provided		criteria provided, single submitter	not provided