Submissions for variant NM_000540.3(RYR1):c.14100G>T (p.Gly4700=)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004014699	SCV004827624	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2024-05-14	criteria provided, single submitter	clinical testing	This synonymous variant causes a G>T nucelotide change in exon 96 of the RYR1 gene. Splice site prediction tools suggest that this variant may have an impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV004733659	SCV005345792	uncertain significance	RYR1-related disorder	2024-03-15	no assertion criteria provided	clinical testing	The RYR1 c.14100G>T variant is not predicted to result in an amino acid change (p.=). However, this variant is predicted to create a strong donor splice site within the exon and may result in aberrant splicing (SpliceAI, Jaganathan K, et al. 2019. PubMed ID: 30661751). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.