Description
Variant summary: This c.473T>G variant affects a conserved nucleotide, resulting in amino acid change from Val to Gly. 3/4 in-silico tools predict this variant to be damaging; however, results from in silico prediction are not definitive. This variant was found in 674/124228 control chromosomes including the broad and large populations from ExAC at a frequency of 0.0054255, which is more than 216 times greater than the maximal expected frequency of a pathogenic allele (0.000025) in this gene, suggesting this variant is benign. In addition, three homozygotes have also been reported from the European (Non-Finnish) population from ExAC, further supporting its benign outcome for the dominant disorders associated with this gene. This variant has been reported in literature in many patients with varying cardiological phenotypes, namely ARVD, DCM, Brugada Syndrome, and Arrhythmia; however, without strong evidence for causality. Rather, this variant was reported to co-occur with DSG2 R46Q and PKP2 p.L452X, supporting for a benign outcome. The variant has also been reported in an unaffected relative of an ARVD family, suggesting a lack of cosegregation (Syrris_2007). Multiple clinical labs have classified this variant as benign/likely benign. Taken together, this variant has been classified as Benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
