Description
Variant summary: GYS1 c.678+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. The TraP (transcript-inferred pathogenicity) in silico prediction tool scores the variant as probably pathogenic. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251360 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.678+1G>A in individuals affected with GYS1-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. However, a different variant affecting the same nucleotide, c.678+1G>C, has been reported in a homozygous individual with adult-onset myopathy without cardiomyopathy (PMID: 35641353). Two ClinVar submitters (evaluation after 2014) have cited the variant, and both submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |