ClinVar

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Asp122Tyr variant in SLC22A5 has been reported in the heterozygous state in 2 individuals with suspected primary carnitine deficiency: a 19 y/o female with cardiomyopath y/myopathy (Li 2010;), and an infant who had an abnormal newborn screen with hyp otonia and low plasma carnitine (ARUP db: http://www.arup.utah.edu/database/octn 2/OCTN2_display.php). However, a second variant in SLC22A5 was not detected in e ither individual. The p.Asp122Tyr variant has also been identified in 0.1% (10/1 3986) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs201082652); however this frequency is not hi gh enough to rule out a pathogenic role. Functional studies in cellular models ( Toh 2011), as well as computational prediction and conservation tools, provide s ome evidence that the variant may impact protein function. However, these types of functional data are not sufficient to determine pathogenicity. In summary, wh ile there is some suspicion for a pathogenic role, the clinical significance of the p.Asp122Tyr variant is uncertain due to the absence of a second pathogenic v ariant in SLC22A5 in affected individuals and limited functional data.