Table 2.
Unpublished variants of uncertain clinical significance identified in KCNJ11 (NM_000525.3)
| Protein change | Nucleotide position | Mutation type | Phenotype | Zygosity | Inheritance | GnomAD MAF | Reporting laboratory |
|---|---|---|---|---|---|---|---|
| p.(Arg4His) | c.11G>A | Missense | HI | Heterozygous | Unaffected mother | 0.000008066 | Exeter |
| p.(Cys42Tyr) | c.125G>A | Missense | Diabetes | Heterozygous | Not known | 0 | Paris |
| p.(Ala45Ser) | c.133G>T | Missense | Diabetes | Heterozygous | Unaffected parent | 0 | Exeter |
| p.(Arg50Trp) | c.148C>T | Missense |
Later‐onset diabetes/HI |
Heterozygous/ Homozygous/ Heterozygous |
Affected parent/ Not known/ Unaffected father |
0 |
Paris/ Paris/ Exeter |
| p.(Gln52Pro) | c.155A>C | Missense | NDM | Heterozygous | Not known | 0 | Exeter |
| p.(Asp58Val) | c.173A>T | Missense | HI | Heterozygous | Unaffected father | 0 | Paris |
| p.(Phe60Ser) | c.179T>C | Missense | HI |
Heterozygous (in cis with VUS) |
Unaffected mother | 0 | Chicago |
| p.(Leu84Arg) | c.251T>G | Missense | HI | Homozygous | Bi‐parental | 0 | Exeter |
| p.(Ala96Val) | c.287C>T | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(His97Tyr) | c.289C>T | Missense | Diabetes | Heterozygous | Unaffected parent | 0 | Exeter |
| p.(Ile114Thr) | c.341T>C | Missense | Diabetes | Heterozygous | Not known | 0 | Paris |
| p.(His115Leu) | c.344A>T | Missense | HI | Heterozygous | Unaffected father | 0 | Paris |
| p.(Ser118Leu) | c.353C>T | Missense | Diabetes | Heterozygous/Heterozygous |
Not known/ Not known |
0.00002389 |
Paris/ Chicago |
| p.(Phe121Ser) | c.362T>C | Missense | HI | Heterozygous | Unaffected father | 0 | Paris |
| p.(Ile131dup) | c.391_393dup | In‐Frame duplication | HI | Homozygous | Bi‐parental | 0 | Paris |
| p.(Ile131Val) | c.391A>G | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(Thr139Pro) | c.415A>C | Missense | HI |
Heterozygous (in cis with VUS) |
Unaffected father | 0 | Paris |
| p.(Glu140Lys) | c.418G>A | Missense | HI | Homozygous | Bi‐parental | 0 | Paris |
| p.(Cys142Tyr) | c.425G>A | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(Val155Leu) | c.463G>T | Missense | HI | Heterozygous | Unaffected mother | 0 | Exeter |
| p.(Val155Met) | c.463G>A | Missense | Diabetes |
Heterozygous/ Heterozygous |
Not known/ Not known |
0.00001199 |
Chicago/ Paris |
| p.(Leu157Val) | c.469C>G | Missense | HI | Heterozygous | Unaffected mother | 0 | Exeter |
| p.(Asn160Lys) | c.480C>G | Missense | HI | Heterozygous | Not known | 0 | Paris |
| p.(Ile167Val) | c.499A>G | Missense | HI |
Heterozygous (in cis with VUS) |
Unaffected father | 0 | Paris |
| p.(Thr171Asn) | c.512C>A | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(Thr180Ile) | c.539C>T | Missense | HI | Heterozygous | Unaffected father | 0 | Paris |
| p.(Ser208Asn) | c.623G>A | Missense | Diabetes | Heterozygous | Not known | 0 | Paris |
| p.(Lys222Gln) | c.664A>C | Missense | HI | Heterozygous | Unaffected mother | 0.00001064 | Exeter |
| p.(Ser265Ile) | c.794G>T | Missense | HI | Heterozygous | Unaffected father | 0.000003978 | Exeter |
| p.(Tyr268His) | c.802T>C | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(Asp274His) | c.820G>C | Missense | HI | Heterozygous | Unaffected father | 0 | Exeter |
| p.(Leu287Pro) | c.860T>C | Missense | HI | Heterozygous | Unaffected father | 0 | Paris |
| p.(Thr297Asn) | c.890C>A | Missense | NDM | Heterozygous | Unaffected parent | 0 | Exeter |
| p.(Ala300Asp) | c.899C>A | Missense | HI | Heterozygous | Not known | 0 | Paris |
| p.(Leu310Pro) | c.929T>C | Missense | HI | Heterozygous | Not maternal | 0 | Exeter |
| p.(Ile318Val) | c.952A>G | Missense | Diabetes | Heterozygous | Not known (affected sibling also heterozygous) | 0.00001061 | Paris |
| p.(Arg325Ser) | c.973C>A | Missense | HI |
Heterozygous (in cis with VUS) |
Unaffected mother | 0.00001591 | Chicago |
| p.(Arg325His) | c.974G>A | Missense | HI | Heterozygous | Unaffected father | 0.00001591 | Exeter |
| p.(Thr336Ala) | c.1006A>G | Missense | Diabetes | Heterozygous | Not known | 0 | Exeter |
| p.(Leu343Val) | c.1027C>G | Missense | NDM | Heterozygous | Unaffected parent | 0 | Exeter |
| p.(Arg369Ser) | c.1105C>A | Missense | Diabetes | Heterozygous | Not known | 0.00003988 | Paris |
| p.(Arg369His) | c.1106G>A | Missense | Diabetes | Heterozygous | Unaffected parent | 0.000003989 | Exeter |
| p.(Arg369Leu) | c.1106G>T | Missense | HI | Heterozygous | Paternal | 0.000003989 | Chicago |
| p.(Ala376Ser) | c.1126G>T | Missense | HI | Heterozygous | Maternal | 0 | Paris |
| p.(Pro380_Lys381dup) | c.1138_1143dup | In‐Frame duplication | Diabetes | Heterozygous | Not known | 0.00007098 | Paris |
Note: The phenotype column highlights a new phenotype; the reporting laboratory column indicates which laboratory has identified the variant in a patient with the new phenotype. See Supporting Information data for details of inclusion criteria for variants in this table.
Abbreviations: HI, hyperinsulinism; NDM, neonatal diabetes.