Submissions for variant NM_001457.4(FLNB):c.1945C>T (p.Arg649Ter)

dbSNP: rs80356517

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília	RCV000020443	SCV000223901	pathogenic	Spondylocarpotarsal synostosis syndrome	2015-04-01	criteria provided, single submitter	research
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000020443	SCV001150104	pathogenic	Spondylocarpotarsal synostosis syndrome	2019-05-27	criteria provided, single submitter	clinical testing
DASA	RCV002298447	SCV002588783	pathogenic	FLNB-Related Spectrum Disorders	2022-11-03	criteria provided, single submitter	clinical testing	The c.1945C>T;p.Arg649* variant creates a premature translational stop signal in the FLNB gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 21280; PMID: 26380986) - PS4. The variant is present at low allele frequencies population databases (rs80356517 – gnomAD 0.00003983%; ABraOM 0.000427 frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005089286	SCV005834912	pathogenic	not provided	2024-10-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg649*) in the FLNB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNB are known to be pathogenic (PMID: 14991055). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive spondylocarpotarsal synostosis syndrome (PMID: 14991055). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21280). For these reasons, this variant has been classified as Pathogenic.
GeneReviews	RCV000020443	SCV000040859	not provided	Spondylocarpotarsal synostosis syndrome		no assertion provided	literature only
Department of Pediatrics, Taizhou Central Hospital, Taizhou University Hospital	RCV000020443	SCV005045302	pathogenic	Spondylocarpotarsal synostosis syndrome	2024-02-01	no assertion criteria provided	clinical testing