Submissions for variant NM_004998.4(MYO1E):c.2481-12A>G

gnomAD frequency: 0.00001  dbSNP: rs370209627

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Biology Laboratory, Fundació Puigvert	RCV001281187	SCV001425109	likely pathogenic	Focal segmental glomerulosclerosis 6	2020-02-01	criteria provided, single submitter	research
Ambry Genetics	RCV003373089	SCV004086660	uncertain significance	Inborn genetic diseases	2023-08-07	criteria provided, single submitter	clinical testing	The c.2481-12A>G intronic alteration results from an A to G substitution 12 nucleotides before coding exon 23 of the MYO1E gene. Based on data from gnomAD, the G allele has an overall frequency of 0.001% (3/282096) total alleles studied. The highest observed frequency was 0.002% (3/128974) of European (non-Finnish) alleles. This variant has been confirmed in trans with a MYO1E pathogenic variant in an individual with clinical features of MYO1E-related focal segmental glomerulosclerosis (Domingo-Gallego, 2022). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.