Submissions for variant NM_001271208.2(NEB):c.13788+1G>A (rs1553862061)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000544699	SCV000640579	pathogenic	Nemaline myopathy 2	2019-11-29	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 89 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 been observed in individuals affected with nemaline myopathy (PMID: 25205138, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 465492). 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). For these reasons, this variant has been classified as Pathogenic.