Submissions for variant NM_000540.3(RYR1):c.3823A>G (p.Thr1275Ala)

dbSNP: rs1568469574

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678326	SCV000804387	uncertain significance	Central core myopathy; Malignant hyperthermia, susceptibility to, 1	2017-10-04	criteria provided, single submitter	provider interpretation	This variant was identified in a 3 year old male with autism spectrum disorder, global developmental delay, hypotonia, and plagiocephaly. It was inherited from a healthy father with no relevant history of developmental or neuromuscular disorder. This variant is absent from the gnomAD database and computational models predict the variant to be damaging. This variant has not been reported previously in the literature, to our knowledge. A second likely pathogenic variant was identified in trans, but clinical correlation with recessive RYR1-related disorders was thought to be poor.
GeneDx	RCV001766453	SCV001989090	uncertain significance	not provided	2019-09-27	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge