Submissions for variant NM_032790.4(ORAI1):c.391G>A (p.Val131Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV003412566	SCV004123253	uncertain significance	Myopathy, tubular aggregate, 2	2023-07-26	criteria provided, single submitter	clinical testing	The ORAI1 c.391G>A p.(Val131Met) missense variant has not, to our knowledge, been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. The p.Val131Met variant has been shown to segregate with disease. Based on the available evidence, the c.391G>A (p.Val131Met) variant is classified as a variant of uncertain significance for tubular aggregate myopathy.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003778363	SCV004589281	likely pathogenic	Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2	2023-08-01	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 131 of the ORAI1 protein (p.Val131Met). This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individual(s) with clinical features of ORAI1-related conditions (Invitae). In at least one individual the variant was observed to be de novo.