TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28887	86884;86885;86886	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
N2AB	27246	81961;81962;81963	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
N2A	26319	79180;79181;79182	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
N2B	19822	59689;59690;59691	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
Novex-1	19947	60064;60065;60066	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
Novex-2	20014	60265;60266;60267	chr2:178559473;178559472;178559471	chr2:179424200;179424199;179424198
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-98
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.1499
• Predicted PPI site: N

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
A/T	rs1377533598	None	0.928	N	0.709	0.222	0.18274738541	gnomAD-4.0.0	2.73696E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59805E-06	0	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
A/C	0.834	likely_pathogenic	0.8389	pathogenic	-0.616	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
A/D	0.8841	likely_pathogenic	0.8718	pathogenic	-0.604	Destabilizing	0.996	D	0.713	prob.delet.	N	0.492487066	None	None	N
A/E	0.8282	likely_pathogenic	0.8129	pathogenic	-0.624	Destabilizing	0.992	D	0.738	prob.delet.	None	None	None	None	N
A/F	0.7019	likely_pathogenic	0.6986	pathogenic	-0.674	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
A/G	0.2984	likely_benign	0.3067	benign	-0.878	Destabilizing	0.963	D	0.646	neutral	N	0.484099656	None	None	N
A/H	0.914	likely_pathogenic	0.9078	pathogenic	-0.9	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
A/I	0.5377	ambiguous	0.5592	ambiguous	-0.112	Destabilizing	0.745	D	0.653	neutral	None	None	None	None	N
A/K	0.9402	likely_pathogenic	0.9298	pathogenic	-0.891	Destabilizing	0.992	D	0.739	prob.delet.	None	None	None	None	N
A/L	0.4986	ambiguous	0.5133	ambiguous	-0.112	Destabilizing	0.895	D	0.572	neutral	None	None	None	None	N
A/M	0.4885	ambiguous	0.5035	ambiguous	-0.188	Destabilizing	0.996	D	0.712	prob.delet.	None	None	None	None	N
A/N	0.7008	likely_pathogenic	0.709	pathogenic	-0.647	Destabilizing	0.997	D	0.726	prob.delet.	None	None	None	None	N
A/P	0.851	likely_pathogenic	0.8476	pathogenic	-0.243	Destabilizing	0.996	D	0.736	prob.delet.	N	0.477731044	None	None	N
A/Q	0.8062	likely_pathogenic	0.8	pathogenic	-0.765	Destabilizing	0.997	D	0.737	prob.delet.	None	None	None	None	N
A/R	0.9206	likely_pathogenic	0.9011	pathogenic	-0.569	Destabilizing	0.992	D	0.744	deleterious	None	None	None	None	N
A/S	0.1607	likely_benign	0.1742	benign	-1.022	Destabilizing	0.928	D	0.635	neutral	N	0.440596808	None	None	N
A/T	0.2484	likely_benign	0.2587	benign	-0.942	Destabilizing	0.928	D	0.709	prob.delet.	N	0.455603546	None	None	N
A/V	0.2962	likely_benign	0.3127	benign	-0.243	Destabilizing	0.085	N	0.364	neutral	N	0.436671069	None	None	N
A/W	0.9636	likely_pathogenic	0.9566	pathogenic	-1.02	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
A/Y	0.8401	likely_pathogenic	0.8311	pathogenic	-0.588	Destabilizing	0.992	D	0.723	prob.delet.	None	None	None	None	N

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.