TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33472	100639;100640;100641	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
N2AB	31831	95716;95717;95718	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
N2A	30904	92935;92936;92937	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
N2B	24407	73444;73445;73446	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
Novex-1	24532	73819;73820;73821	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
Novex-2	24599	74020;74021;74022	chr2:178536333;178536332;178536331	chr2:179401060;179401059;179401058
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-131
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.8905
• 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
L/R	None	None	0.999	N	0.63	0.524	0.720044110252	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85835E-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
L/A	0.2374	likely_benign	0.3062	benign	-0.341	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	I
L/C	0.7755	likely_pathogenic	0.8034	pathogenic	-0.67	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	I
L/D	0.7334	likely_pathogenic	0.816	pathogenic	0.041	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
L/E	0.4644	ambiguous	0.586	pathogenic	-0.06	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
L/F	0.2508	likely_benign	0.2919	benign	-0.526	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
L/G	0.6735	likely_pathogenic	0.7431	pathogenic	-0.447	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	I
L/H	0.4429	ambiguous	0.5367	ambiguous	0.126	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
L/I	0.0991	likely_benign	0.1187	benign	-0.196	Destabilizing	0.992	D	0.389	neutral	N	0.439076656	None	None	I
L/K	0.4658	ambiguous	0.5894	pathogenic	-0.117	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
L/M	0.1642	likely_benign	0.1837	benign	-0.351	Destabilizing	0.985	D	0.394	neutral	None	None	None	None	I
L/N	0.4955	ambiguous	0.5947	pathogenic	0.03	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	I
L/P	0.4259	ambiguous	0.5043	ambiguous	-0.215	Destabilizing	1.0	D	0.644	neutral	N	0.447965498	None	None	I
L/Q	0.2728	likely_benign	0.3522	ambiguous	-0.163	Destabilizing	0.999	D	0.643	neutral	N	0.457083626	None	None	I
L/R	0.3828	ambiguous	0.4789	ambiguous	0.332	Stabilizing	0.999	D	0.63	neutral	N	0.445039836	None	None	I
L/S	0.3494	ambiguous	0.4344	ambiguous	-0.394	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	I
L/T	0.2425	likely_benign	0.3252	benign	-0.388	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	I
L/V	0.1406	likely_benign	0.1607	benign	-0.215	Destabilizing	0.992	D	0.438	neutral	N	0.449522936	None	None	I
L/W	0.4542	ambiguous	0.504	ambiguous	-0.546	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
L/Y	0.5419	ambiguous	0.6203	pathogenic	-0.278	Destabilizing	1.0	D	0.625	neutral	None	None	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.