Table 1.

Table summarizing clinical features, variants, and testing results for patients with a clinical phenotype of a STS.

Case no.	Age/sex	Clinical features	Significant family history (yes/no)a	FlowFISH TL (centile length in granulocytes/ lymphocytes)	Gene	cDNA change	Protein change	Protein region	In silico predictions (SIFT/PolyPhen)	CADD score	3D model prediction	Conclusion from TRAP assay	ACMG classification (at the clinical report/after research testing)
1b	23/M	Premature graying of hair, macrocytosis, thrombocytopenia, bilateral hip avascular necrosis	Yes	<1st/<1st	TERT	c.2768 C > T	p.Pro923Leu	Reverse-transcriptase domain	Deleterious/probably damaging	24.2	Destabilizes structure	NA	Pathogenic/pathogenic
2	69/F	Premature graying of hair, IPF, anemia, leukopenia	No	10th/10th	TERT	c.3362 C > T	p.Pro1121Leu	C-terminal extension	Deleterious/probably damaging	22.9	Destabilizes structure	Absent telomerase function	VUS/likely pathogenic
3	27/F	Macrocytosis, neutropenia	No	<1st/1st	TERT	c.1765A > C	p.Ile589Leu	None described	Tolerated/benign	5.08	Neutral	Decreased telomerase function	VUS/likely pathogenic
4	19/M	Macrocytosis	No	<1st/<1st	TERT	c.1885G > A	p.Gly629Arg	Reverse-transcriptase domain	Deleterious/probably damaging	23.1	NA	Decreased telomerase function	VUS/pathogenic
5	47/M	IPF, pancytopenia	No	<1st/<1st	TERC	n.238 G > C	NA	NA	NA	NA	Changes TERC organization	NA	VUS/pathogenic

FISH fluorescence in situ hybridization, IPF idiopathic pulmonary fibrosis, NA not applicable, STS short telomere syndrome, TL telomere length, TRAP telomerase repeated amplification protocol.

^aSignificant family history was defined as the presence of one or more first- or second-degree relatives with one or more clinical features characteristic of STSs, such as premature onset of hair graying (age < 30 years), IPF, cryptogenic cirrhosis or nodular regenerative hyperplasia, or unexplained cytopenias.

^bClinical history of this case were previously published; however, functional testing results are new.