Submissions for variant NM_130837.3(OPA1):c.610+360G>A

dbSNP: rs1553872542

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592332	SCV000700900	uncertain significance	not provided	2016-12-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000592332	SCV004034038	likely pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	OPA1: PM2, PS3:Moderate, PS4:Moderate
Genomics England Pilot Project, Genomics England	RCV001542572	SCV001760117	pathogenic	Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530650	SCV004710022	uncertain significance	OPA1-related disorder	2023-12-24	no assertion criteria provided	clinical testing	The OPA1 c.610+360G>A variant is predicted to interfere with splicing. This variant is located in a deep intronic region (intron 4b) and has been reported in two patients with optic atrophy without extraocular neurodegeneration (Bonifert et al. 2014. PubMed ID: 24970096). Of note, another variant in this region (c.610+364G>A), has also been reported in patients with optic atrophy. Functional studies of the c.610+360G>A and c.610+364G>A showed that both variants introduce a cryptic splice site which leads to aberrant splicing of OPA1. Additional data to support the pathogenicity of the c.610+360G>A variant was not provided (Bonifert et al. 2014. PubMed ID: 24970096). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.