Table 4.
Genes with Variants Reported as Pathogenic or Likely Pathogenic More than Once
| Gene | Variants Reported | Disorder | Condition Category | Variant Category | Classification | No. of heterozygotes (n = 202) | Frequency of Disorder in Study (n = 202) | Carrier Frequency (%)a |
|---|---|---|---|---|---|---|---|---|
| HFE (MIM: 613609) | NM_000410.3 (c.845G>A [p.Cys282Tyr]) | hereditary hemochromatosis (MIM: 235200) | adult onset | Known | pathogenic | 30 | 20% | 6%–13% |
| NM_000410.3 (c.187C>G [p.His63Asp])b | Known | pathogenic | 10 | |||||
| GJB2 (MIM: 121011) | NM_004004.5 (c.35delG [p.Gly12Valfs∗2]) | nonsyndromic, hearing loss (MIM: 220290) | mild | Known | pathogenic | 3 | 9% | 2.3% |
| NM_004004.5 (c.35dupG [p.Val13Cysfs]) | Known | pathogenic | 1 | |||||
| NM_004004.5 (c.109G>A [p.Val37Ile]) | Known | likely pathogenic | 4 | |||||
| NM_004004.5 (c.−23+1G>A) | Known | pathogenic | 1 | |||||
| NM_004004.5 (c. 101T>C [p.Met34Thr]) | Known | likely pathogenic | 4 | |||||
| NM_004004.5 (c.269T>C [p.Leu90Pro]) | Known | pathogenic | 3 | |||||
| NM_004004.5 (c.416G>A [p.Ser139Asn]) | Known | likely pathogenic | 1 | |||||
| NM_004004.5 (c.−22−2A>C) | Known | pathogenic | 1 | |||||
| F5 (MIM: 612309) | NM_000130.4 (c.1601G>A [p.Arg534Gln]) | factor V Leiden thrombophilia (MIM: 227400) | unpredictable | known | pathogenic | 17 | 8% | 3%–8% |
| SERPINA1 (MIM: 107400) | NM_001127700.1 (c.1096G>A [p.Glu366Lys]) | alpha-1 antitrypsin deficiency (MIM: 613490) | adult onset | known | pathogenic | 6 | 6% | 2.4%–4.8% |
| NM_001127700.1 (c.863A>T [p.Glu288Val]) | known | pathogenic | 6 | |||||
| ABCA4 (MIM: 601691) | NM_000350.2 (c.6089G>A [p.Arg2030Gln]) | cone rod dystrophy 3 (MIM: 604116); Stargardt disease (MIM: 248200) | mild | known | pathogenic | 1 | 4% | 2% |
| NM_000350.2 (c.1964T>G [p.Phe655Cys]) | known | likely pathogenic | 2 | |||||
| NM_000350.2 (c.4139C>T [p.Pro1380Leu]) | known | pathogenic | 1 | |||||
| NM_000350.2 (c.2588G>C [p.Gly863Ala]) | known | likely pathogenic | 2 | |||||
| NM_000350.2 (c.5882G>A [p.Gly1961Glu]) | known | pathogenic | 3 | |||||
| CYP21A2c (MIM: 613815) | NM_000500.8 (c.1360C>T [p.Pro454Ser]) | congenital adrenal hyperplasia (MIM: 201910) | serious | known | pathogenic | 3 | 4%d | 1.6%–6%e |
| NM_000500.8 (c.844G>T [p.Val282Leu]) | known | pathogenic | 3 | |||||
| NM_000500.8 (c.955C>T [p.Gln319Ter]) | known | pathogenic | 2 | |||||
| CFTR (MIM: 602421) | NM_000492.3 (c.1521_1523delCTT [p.Phe508delPhe]) | cystic fibrosis (MIM: 219700) | serious | known | pathogenic | 6 | 3% | 4% |
| SPG7 (MIM: 602783) | NM_003119.3 (c.1529C>T [(p.Ala510Val)) | spastic paraplegia 7 (MIM: 607259) | adult onset | known | pathogenic | 3 | 2% | 0.9%–1.5% |
| NM_003119.3 (c.1045G>A [p.Gly349Ser]) | known | pathogenic | 2 |
All variants use the HGVS nomenclature.
Source: GeneReviews or Genetics Home Reference.
The H63D variant in HFE was analyzed and reported only if the partner was a carrier of GenBank: NM_000410.3 (c.845G>A [p.Cys282Tyr]).
The coding DNA nomenclature is used instead of the protein sequence nomenclature to avoid the discrepancy associated with the latter when using the hg19 genomic reference sequence; the coding DNA is also used for nomenclature for splice/intronic variants; one participant was homozygous for the SERPINA1 GenBank: NM_001127700.1 (c.1096G>A [p.Glu366Lys]) allele and was excluded from the table.
Combined classic and non-classic with 3% carrying a variant for the non-classic form and 1% carrying a variant for the classic form.
Combined frequency for classic and non-classic form; most of these variants were observed more than once.