Table 1.

PARN Rare Variants Identified by Whole-Exome Sequencing

Variant Type	Variant (Protein)	Variant (DNA)	Splicing Effect	ExAC DB Frequency	PP2	Affected Carrier Telomere %	Segregates with Disease
Loss of function variants
Frameshift	p.Thr296SerfsX14	c.887_888delCA	NA	None	NA	2%, 3%	Yes
Splice	NA	c.620+5G>A	Yes	None	NA	1%	Yes
Nonsense	Glu189Stop	c.565G>T	NA	None	NA	1%, 1%, 12%	Yes
Frameshift	p.Phe418PhefsX6	c.1251delT	NA	None	NA	15%	No*
Variants of uncertain significance
Missense	Asn7His	c.19A>C	Unknown	None	1	3%	Yes
Missense	Lys56Asn	c.168G>C	NA	G=1/C=66,604	0.667	5%, 5%	Yes
Intron	NA	c.178-3C>T	No	None	NA	7%, 9%	Yes
Intron	NA	c.703-11_703-10delAT	Unknown	None	NA	1%, 2%	Yes
Intron	NA	c.245+75_245+77delCCC	Unknown	NA	NA	15%	No*
Synonymous	Ala153Ala	c.459G>C	Unknown	None	NA	21%, 22%	No†
Intron	NA	c.840+6T>C	Unknown	G=33/A=66,636	NA	1%	No‡
Intron	NA	c.1006-11G>A	Unknown	G=3/A=65,604	NA	1%, 2%	Yes¶
Missense	Ser498Asn	c.1493G>A	NA	G=20/A=60,728	0.996	1%	No

Definition of abbreviations: ExAC DB = Exome Aggregation Consortium database; NA = not applicable; PARN = polyadenylation-specific RNase deadenylation nuclease; PP2 = PolyPhen2; TERT = telomerase reverse transcriptase.

^*p.Phe418PhefsX6 was not detected in one affected participant; however, this subject carried an intronic variant of uncertain significance, c.245+75_245+77delCCC.

^†One subject did not carry c.459G but had a family history of idiopathic pulmonary fibrosis in both parental lines.

^‡Two subjects did not carry c.840+6T>C; however, they had a family history of idiopathic pulmonary fibrosis in both parental lineages.

^¶This family also has a novel segregating TERT variant Thr839Lys.