Submissions for variant NM_001271208.2(NEB):c.13369-6_13372delinsGGCATT

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001240278	SCV001413209	likely pathogenic	Nemaline myopathy 2	2019-10-25	criteria provided, single submitter	clinical testing	This variant results in the deletion of part of exon 88 (c.13369-6_13372delinsGGCATT), and affects acceptor splice site in intron 87 of the NEB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant occurs in a region of NEB (Exons 82-105) consisting of three highly homologous 8-exon repeat units (exons 82-89, exons 90-97, exons 98-105). Sequence variants in this region can be detected, but this assay cannot determine which of the three repeat units is affected, and zygosity is often ambiguous. All variants in this region are reported relative to the exon 82-89 repeat. This variant has not been reported in the literature in individuals with NEB-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.