Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders

Table 2 Germline variants identified in patients with telomere biology disorders

ID	Gene	Nucleotide change^a	Amino acid change^a	Inheritance	MAF^b	Carriers (overall / Finland)^b	Affected domain^c, **	REVEL score^d, **	Classification^e	Reference
P1.1	DKC1	c.1218_1219insCAG	p.(Asp406_Ser407insGln)	XLR^f	–	–	–	–	Likely pathogenic	novel
P1.2	DKC1	c.1218_1219insCAG	p.(Asp406_Ser407insGln)	XLR^f	–	–	–	–	Likely pathogenic	novel
P2	TERT	c.2051A > G	p.(Asp684Gly)	AR	0.0015	27/25	Reverse transcriptase domain	0.548	Uncertain significance	novel
P2	TERT	c.3202G > A	p.(Glu1068Lys)	AR	–	–	–	0.546	Uncertain significance	novel
P3	RTEL1	c.1721G > C	p.Arg574Pro	AR	4.08E-06	1/0	ATP-dependent helicase, C-terminal; P-loop containing nucleoside triphosphate hydrolase	0.752	Likely pathogenic	novel
P3	RTEL1	c.3724_3725delTG	p.(Cys1242Cysfs^f18)	AR	8.20E-06	2/1	–	–	Pathogenic	novel

Abbreviations: F, female; M, male; XLR, X-linked recessive, autosomal recessive; MAF, minor allele frequency
**data retrieved with Annovar; AR
DKC1 gene reference sequences (Ensembl): ENSG00000130826; ENST00000369550
TERT gene reference sequences (Ensembl): ENSG00000164362; ENST00000296820
RTEL1 gene reference sequences (Ensembl): ENSG00000258366; ENST00000318100
^alocation according to RefSeq
^bminor allele frequency according to gnomAD database**
^cInterPro database**
^dREVEL pathogenicity score** [26]
^eestimated according to the ACMG Standards and Guidelines [17]
^fmale

ISSN: 1750-1172