Table 2.
List of 30 Candidate Deleterious Germline Mutations in Familial and Sporadic LC Cases
| Region | Disease association |
Gene | Marker * | SNV/Indels | Ref./Alt. | RS ID | MAF in KG/ESP | CADD C-score # |
N mutated Familial vs. Sporadic |
Total N mutated LC cases |
|---|---|---|---|---|---|---|---|---|---|---|
| 10q25.1 | LC+SM+PF | CCDC147 | 10:106163533-SNV | p.Arg696Cys | C/T | rs41291850 | 0.0026/0.0072 | 16.2 | 2 : 1 | 3 |
| 9q34.2 | SM | DBH | 9:136501569-SNV | p.Val26Met | G/A | rs76856960 | 0.0034/0.0045 | 17.3 | 0 : 2 & | 3 |
| 9:136522317-SNV | p.Met563Thr | T/C | rs201973877 | 0.0002/0.0002 | 20.3 | 1 : 0 | ||||
| 15q25.1 | LC+SM+PF+COPD | IREB2 | 15:78783019-SNV | p.Gly747Glu | G/A | rs139092247 | 0.0014/0.0034 | 35 | 1 : 0 | 3 |
| CHRNA5 | 15:78880766-SNV | g. splice donor | G/A | rs200616965 | NA | 22.7 | 0 : 1 & a | |||
| CHRNB4 | 15:78921343-SNV | p.Ala435Val | G/A | rs56317523 | 0.0008/0.0028 | 27.2 | 1 : 0 | |||
| 16q23.1 | PF | KARS | 16:75665388-SNV | p.Arg421Gln | C/T | rs149772470 | 0.0002/0.0018 | 26.1 | 0 : 1 & | 3 |
| 16:75665146-SNV | p.Arg448Cys | G/A | rs77573084 | 0.0006/0.0030 | 19.6 | 0 : 1 & a | ||||
| WWOX | 16:78466521-SNV | p.Arg310Cys | C/T | rs193001955 | 0.0006/0.0006 | 24.1 | 0 : 1 & | |||
| 1q44 | SM | C1orf100 | 1:244541827-SNV | p.Asp71His | G/C | rs41269385 | 0.0022/0.0065 | 14.2 | 2 : 0 | 2 |
| 2q35 | PF | TNS1 | 2:218686643-SNV | p.Glu1027Val | T/A | rs112371945 | 0.0006/0.0013 | 22.7 | 1 : 0 | 2 |
| 2:218669288-SNV | p.Thr1701Met | G/A | rs61740054 | 0.0010/0.0034 | 27.9 | 0 : 1 & | ||||
| 5q32 | LC+PF | FBXO38 | 5:147817940-SNV | p.Pro893Arg | C/G | rs141168806 | NA/0.0001 | 22.9 | 1 : 0 | 2 |
| 5:147821690-SNV | p.Val1108Ile | G/A | rs143682696 | 0.0002/0.0008 | 26.4 | 1 : 0 | ||||
| 7q31.1 | SM | PNPLA8 | 7:108154659-SNV | p.Cys379Gly | A/C | rs141089628 | 0.0002/0.0033 | 15.1 | 0 : 1 & | 2 |
| 7:108137944-SNV | p.Ile479Ser | A/C | Novel | NA | 25.2 | 1 : 0 | ||||
| 10q23.31 | LC+SM+COPD | PANK1 | 10:91359156-SNV | p.Phe163Ser | A/G | Novel | NA | 26.1 | 1 : 0 | 2 |
| IDE | 10:94243061-SNV | p.Asp9Asn | C/T | Novel | NA | 36 | 0 : 1 & b | |||
| 13q12.12 | LC | MIPEP | 13:24448998-SNV | p.Leu197Pro | A/G | rs150167906 | 0.0002/0.0023 | 21.4 | 1 : 1 | 2 |
| 14q22.1 | PF | NID2 | 14:52508948-SNV | p.Thr567Met | G/A | rs150406341 | 0.0006/0.0060 | 19.3 | 1 c : 1 & a | 2 |
| 17q24.2 | LC+PF | BPTF | 17:65889520-SNV | p.Arg823Gln | G/A | rs375975293 | NA/0.0001 | 19.8 | 1 : 0 | 2 |
| 17:65936627-SNV | p.Thr2237Met | C/T | rs372551122 | NA | 17.2 | 0 : 1 & | ||||
| 5q33.1 | LC+PF | MYOZ3 | 5:150051315-SNV | g. splice acceptor | A/G | rs143036945 | 0.0002/0.0005 | 12.3 | 0 : 1 | 1 |
| 10q22.2–3 | PF | C10orf11 | 10:77542754-Deletion | p.Ser8 Frameshift | C/− | rs146123023 | 0.007/0.0013 | NA | 1 : 0 | 1 |
| 12q13.3 | PF | LRP1 | 12:57577915-SNV | p.Arg1993Trp | C/T | rs141826184 | 0.0004/0.0031 | 21.8 | 0 : 1 & | 1 |
| 12q21.2 | SM | NAV3 | 12:78392209-SNV | p.Ser278Ile | G/T | rs755721519 | NA | 31 | 0 : 1 & b | 1 |
| 14q24.2 | PF | SLC8A3 | 14:70515508-SNV | p.Val152Met | C/T | rs144289733 | 0.0004/0.0008 | 27 | 1 : 0 | 1 |
| 15q15.2 | LC | TGM5 | 15:43527092-SNV | p.Tyr502His | A/G | rs146901531 | 0.0002/0.0006 | 18.8 | 0 : 1 & | 1 |
| 18p11.3 | LC | LAMA1 | 18:6965341-SNV | p.Arg2381Cys | G/A | rs142063208 | 0.0028/0.0016 | 25 | 1 c : 0 | 1 |
| 19q13.2 | LC+SM+PF+COPD | EGLN2 | 19:41307024-SNV | p.Val183Met | G/A | rs117916638 | 0.0002/0.0004 | 16.9 | 1 : 0 | 1 |
*
All are heterozygous mutations.
#
C-score is the overall measure of deleteriousness. C-score ≥ 20 indicates top 1% deleterious in the human genome.
&
Sporadic LC patient(s) with severe COPD;
a,b,c
Indicates the same patients.