Table 1.
Carrier Findings for Well-Known Disease-Associated Variants within Introns
| Gene | Variant | Disorder | Condition Category | Variant Category | Classification |
|---|---|---|---|---|---|
| PTS (MIM: 612719) | NM_000317.2 (c.84_291A>G) | BH4-deficient hyperphenylalaninemia (MIM: 261640) | serious | known | likely pathogenic |
| GAA (MIM: 606800) | NM_001079804.2 (c.−32−13T>G) | glycogen storage disease II (MIM: 232300) | serious | known | pathogenic |
| GJB2 (MIM: 121011) | NM_004004.5 (c.−22−2A>C) | deafness and hearing loss (MIM: 220290) | mild | known | pathogenic |
| NM_004004.5 (c.−23+1G>A) | known | pathogenic | |||
| PYGM (MIM: 608455) | NM_005609.3 (c.425−26A>G) | McArdle disease (MIM: 232600) | unpredictable | known | likely pathogenic |
These variants are not in the canonical splice-site within introns. An a priori knowledge of the mutation spectrum in a gene is not required for using GS-based carrier testing. The variants are annotated according to the Human Genome Variation Society (HGVS)28 recommended nomenclature. The variants in GAA and GJB2 are located in the introns that are upstream (5′ in the coding strand) of the translational start codon (where the adenine position in ATG start codon is +1).