TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8447	25564;25565;25566	chr2:178717535;178717534;178717533	chr2:179582262;179582261;179582260
N2AB	8130	24613;24614;24615	chr2:178717535;178717534;178717533	chr2:179582262;179582261;179582260
N2A	7203	21832;21833;21834	chr2:178717535;178717534;178717533	chr2:179582262;179582261;179582260
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-69
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0899
• 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
L/F	None	None	1.0	N	0.84	0.457	0.61132195657	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9607	likely_pathogenic	0.9513	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/C	0.9522	likely_pathogenic	0.942	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9992	pathogenic	-3.771	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/E	0.9965	likely_pathogenic	0.9949	pathogenic	-3.461	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/F	0.8327	likely_pathogenic	0.7425	pathogenic	-1.954	Destabilizing	1.0	D	0.84	deleterious	N	0.501968207	None	None	N
L/G	0.991	likely_pathogenic	0.988	pathogenic	-3.672	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/H	0.9934	likely_pathogenic	0.9892	pathogenic	-3.247	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.535583051	None	None	N
L/I	0.2621	likely_benign	0.2394	benign	-1.365	Destabilizing	0.997	D	0.595	neutral	N	0.478784616	None	None	N
L/K	0.9944	likely_pathogenic	0.9923	pathogenic	-2.476	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/M	0.4113	ambiguous	0.3412	ambiguous	-1.379	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/N	0.9958	likely_pathogenic	0.9941	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/P	0.997	likely_pathogenic	0.9949	pathogenic	-1.939	Destabilizing	1.0	D	0.899	deleterious	D	0.535583051	None	None	N
L/Q	0.9883	likely_pathogenic	0.9821	pathogenic	-2.873	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/R	0.9872	likely_pathogenic	0.9819	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.916	deleterious	D	0.535583051	None	None	N
L/S	0.9963	likely_pathogenic	0.9948	pathogenic	-3.694	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/T	0.9813	likely_pathogenic	0.9764	pathogenic	-3.235	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/V	0.2902	likely_benign	0.2695	benign	-1.939	Destabilizing	0.998	D	0.595	neutral	N	0.518956017	None	None	N
L/W	0.9773	likely_pathogenic	0.9579	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Y	0.9774	likely_pathogenic	0.9634	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.893	deleterious	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.