TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1311	4156;4157;4158	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
N2AB	1311	4156;4157;4158	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
N2A	1311	4156;4157;4158	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
N2B	1265	4018;4019;4020	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
Novex-1	1265	4018;4019;4020	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
Novex-2	1265	4018;4019;4020	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986
Novex-3	1311	4156;4157;4158	chr2:178779261;178779260;178779259	chr2:179643988;179643987;179643986

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-5
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.62
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
H/P	None	None	1.0	N	0.703	0.635	0.643426271191	gnomAD-4.0.0	6.84211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9942E-07	0	0
H/R	None	None	1.0	N	0.644	0.552	0.423480098753	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31895E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
H/A	0.5719	likely_pathogenic	0.6291	pathogenic	-0.649	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	I
H/C	0.4456	ambiguous	0.468	ambiguous	0.043	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
H/D	0.5109	ambiguous	0.5484	ambiguous	-0.174	Destabilizing	1.0	D	0.707	prob.neutral	N	0.385356097	None	None	I
H/E	0.6242	likely_pathogenic	0.6783	pathogenic	-0.077	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	I
H/F	0.4899	ambiguous	0.5283	ambiguous	0.487	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
H/G	0.685	likely_pathogenic	0.7368	pathogenic	-1.022	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
H/I	0.5413	ambiguous	0.6038	pathogenic	0.376	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
H/K	0.6521	likely_pathogenic	0.7131	pathogenic	-0.403	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
H/L	0.2463	likely_benign	0.2787	benign	0.376	Stabilizing	1.0	D	0.698	prob.neutral	N	0.472316171	None	None	I
H/M	0.72	likely_pathogenic	0.7719	pathogenic	0.168	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
H/N	0.1969	likely_benign	0.2269	benign	-0.473	Destabilizing	0.999	D	0.515	neutral	N	0.447789381	None	None	I
H/P	0.5826	likely_pathogenic	0.6451	pathogenic	0.057	Stabilizing	1.0	D	0.703	prob.neutral	N	0.443067579	None	None	I
H/Q	0.3843	ambiguous	0.4431	ambiguous	-0.245	Destabilizing	1.0	D	0.648	neutral	N	0.444700985	None	None	I
H/R	0.3122	likely_benign	0.3708	ambiguous	-0.922	Destabilizing	1.0	D	0.644	neutral	N	0.435329303	None	None	I
H/S	0.3756	ambiguous	0.422	ambiguous	-0.591	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
H/T	0.4854	ambiguous	0.5574	ambiguous	-0.377	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
H/V	0.4864	ambiguous	0.5484	ambiguous	0.057	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
H/W	0.6629	likely_pathogenic	0.686	pathogenic	0.797	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
H/Y	0.2041	likely_benign	0.2222	benign	0.911	Stabilizing	0.999	D	0.547	neutral	N	0.486766999	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.