Submissions for variant NM_001130987.2(DYSF):c.460+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1278864604

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000665139	SCV000789207	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2017-01-24	criteria provided, single submitter	clinical testing
Invitae	RCV000694014	SCV000822439	pathogenic	Qualitative or quantitative defects of dysferlin	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 5 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). 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. Disruption of this splice site has been observed in individuals with DYSF-related conditions (PMID: 36580222). This variant is also known as c.460+1G>A. ClinVar contains an entry for this variant (Variation ID: 550404). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000665139	SCV004171311	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B		criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000665139	SCV002079752	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2021-03-31	no assertion criteria provided	clinical testing