Submissions for variant NM_001267550.2(TTN):c.103859G>A (p.Arg34620His)

gnomAD frequency: 0.00002  dbSNP: rs367927066

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000215552	SCV000272829	uncertain significance	not specified	2015-04-16	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg32052His v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but been identified in 10/16510 South Asian chromosomes by the Exome Aggregat ion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs367927066). Comput ational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein, though 3 species (parrot, zebrafish, a nd cavefish) has a histidine (His) at this position, suggesting that this change may be tolerated. In summary, while the clinical significance of the p.Arg32052 His variant is uncertain, the presence of the variant amino acid is multiple oth er species suggests that it is more likely to be benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768832	SCV000900205	uncertain significance	Cardiomyopathy	2016-05-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001556986	SCV001778669	likely benign	not provided	2021-02-02	criteria provided, single submitter	clinical testing