Description
Variant summary: GPD1L c.370A>G (p.Ile124Val) results in a conservative amino acid change located in the N-terminal of the Glycerol-3-phosphate dehydrogenase, NAD-dependent domain (IPR011128) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0029 in 277792 control chromosomes in the gnomAD database and publications, including 7 homozygotes. The observed variant frequency is approximately 289-fold of the estimated maximal expected allele frequency for a pathogenic variant in GPD1L causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. The variant, c.370A>G, has been reported in the literature in individuals affected with SIDS, sudden death, and atrial fibrillation (VanNorstrand_2007, Skinner_2014, Husser_2017). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (VanNorstrand_2007). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely 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 |
