Additional Table 1 List of variants in four FPF genes found in affected family members and sporadic patients.
Gene
SFTPC
SFTPA2
Exon/
Intron
intron 1
intron 2
exon 4
intron 4
intron 4
exon 5
exon 6
5'UTR
5'UTR
exon 1
exon 2
intron 2
SIFT
Polyphen
rs4715
rs2070687
rs1124
rs7592
rs17883188
rs17881948
rs2271788
-
Predicted protein
change
NA
NA
p.Thr138Asn
NA
NA
p.Ser186Asn
NA
NA
NA
NA
NA
NA
NA
NA
tolerated
NA
NA
tolerated
NA
NA
NA
NA
NA
NA
-
NA
NA
c.26C>A
rs1059046
p.Thr9Asn
tolerated
exon 3
exon 3
exon 4
exon 4
exon 4
exon 4
exon 4
exon 4
exon 4
c.56C>T
c.148G>C
c.186G>A
c.197C>T
c.198A>G
c.213G>A
c.217A>G
c.241G>A
c.253C>T
rs61862677
rs11554795
rs2434114
rs1713397
-
p.Ala19Val
p.Val50Leu
p.=
p.Thr66Ile
p.=
p.=
p.Asn73Asp
p.Val81Ile
p.Arg85Cys
tolerated
tolerated
NA
tolerated
NA
NA
tolerated
tolerated
tolerated
exon 4
c.271G>C
rs17886395
p.Ala91Pro
tolerated
exon 4
intron 4
intron 4
intron 4
intron 4
intron 4
c.282A>G
c.292+11C>T
c.292+45G>A
c.292+46A>C
c.292+48dupC
c.292+64A>G
rs17886221
rs17884130
rs17882071
rs17880662
p.=
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Variant
rs#
c.42+72C>A
c.43-21T>C
c.413C>A
c.435+14G>A
c.436-8C>G
c.557G>A
c.*123G>A
c.-120T>G
c.-103T>A
c.-73G>C
c.-35T>G
c.-24+62T>C
c.[-23-5G>A];[-235G>T]
exon 3
intron 2
NA
NA
benign
NA
NA
benign
NA
NA
NA
NA
NA
NA
Allele
frequency
0.13 (10/76)
0.33 (19/58)
0.052 (3/58)
0.069 (4/58)
0.12 (7/58)
0.10 (6/58)
0.24 (18/76)
0.93 (106/114)
0.08 (9/114)
0.14 (22/160)
0.91 (42/46)
0.93 (106/114)
European allele
frequency
NA
NA
0.23
NA
0.24
0.29
0.30
0.98
0.06
0.86
NA
NA
NA
0.96 (135/140)
NA
0.73 (104/142)
0.82
0.44 (62/142)
0.19 (6/32)
0.78 (86/110)
0.89 (98/110)
0.89 (98/110)
0.89 (98/110)
0.89 (98/110)
0.85 (94/110)
0.86 (95/110)
NA
0.95
NA
NA
1.00
NA
NA
NA
NA
0.88 (97/110)
0.10
0.86 (95/110)
0.88 (97/110)
0.14 (15/110)
0.14 (15/110)
0.79 (87/110)
0.73 (80/110)
0.02
NA
0.00
0.00
NA
0.00
possibly
damaging
benign
benign
NA
benign
NA
NA
benign
benign
benign
probably
damaging
NA
NA
NA
NA
NA
NA
TERT
†
*
TERC
intron 4
exon 5
intron 5
intron 5
intron 5
exon 6
exon 6
3'UTR
3'UTR
3'UTR
exon 1
exon 2
c.293-68G>A
c.342C>T
c.370+67C>G
c.370+77T>C
c.370+77_78dupTA
c.420C>T
c.667C>A
c.*28G>A
c.*29A>G
c.*120A>G
c.-42dupC
c.1321_1323delGAG
rs1610802
rs61862719
rs1965708
rs17879546
rs17880428
-
NA
p.=
NA
NA
NA
p.=
p.Gln223Lys
NA
NA
NA
NA
p.Glu441del
NA
NA
NA
NA
NA
NA
tolerated
NA
NA
NA
NA
NA
exon 4
exon 9
c.1892G>A
c.2517G>A
-
p.Arg631Gln
p.=
damaging
NA
exon 10
c.2594G>A
rs121918666
p.Arg865His
damaging
exon 10
c.2648T>G
-
p.Phe883Cys
damaging
exon 14
exon 15
exon 16
3'UTR
5'UTR
5'UTR
3'UTR
3'UTR
c.3039C>T
c.3184G>A
c.3324G>A
c.*99C>T
n.-23G>A
n.-11G>A
n.*63A>G
n.*111C>G
rs33954691
rs35719940
rs35033501
rs2853690
rs2293607
-
p.=
p.Ala1062Thr
p.=
NA
NA
NA
NA
NA
NA
tolerated
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
benign
NA
NA
NA
NA
NA
possibly
damaging
NA
possibly
damaging
probably
damaging
NA
benign
NA
NA
NA
NA
NA
NA
0.01 (1/112)
0.07 (8/112)
0.08 (9/112)
0.02 (2/112)
0.10 (11/112)
0.14 (15/112)
0.07 (8/112)
0.02 (2/112)
0.01 (1/112)
0.14 (16/112)
0.01 (1/112)
0.01 (1/112)
0.01 (1/112)
0.04 (2/46)
NA
NA
NA
NA
NA
0.25
0.11
0.02
0.02
NA
NA
NA
NA
NA
0.01 (1/112)
NA
0.01 (1/92)
NA
0.11 (5/46)
0.01 (1/112)
0.04 (2/46)
0.13 (6/46)
0.02 (1/46)
0.01 (1/108)
0.19 (21/108)
0.02 (1/46)
0.14
0.02
0.04
0.16
NA
NA
0.30
NA
NA=Not Available; SIFT=Sorting Intolerant From Tolerant; p.= indicates there is no amino acid change for this coding variant
† This is a rare known variant previously identified in a normal control and shown to be associated with normal telomere length
(Yamaguchi H, Calado RT, Ly H, et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J
Med. 2005;352(14):1413-24).
* This variant was identified as potentially affecting telomerase function in one study (Calado RT, Regal JA, Hills M, et al.
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc Natl Acad Sci U S A.
2009;106(4):1187-92) and was also identified in control populations; however, it appears to be more frequent in PF and AML
populations than controls. We describe this as an unclassified variant as it is in a sporadic PF patient in our cohort. We also do not
know the NL population frequency for the variant nor did we perform telomerase length assays.