TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2764	8515;8516;8517	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
N2AB	2764	8515;8516;8517	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
N2A	2764	8515;8516;8517	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
N2B	2718	8377;8378;8379	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
Novex-1	2718	8377;8378;8379	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
Novex-2	2718	8377;8378;8379	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227
Novex-3	2764	8515;8516;8517	chr2:178770502;178770501;178770500	chr2:179635229;179635228;179635227

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-17
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0591
• 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/V	rs2091305777	None	0.885	D	0.658	0.538	0.863069828929	gnomAD-4.0.0	4.10441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39576E-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	0.9403	likely_pathogenic	0.9654	pathogenic	-2.165	Highly Destabilizing	0.91	D	0.744	deleterious	None	None	None	None	N
L/C	0.907	likely_pathogenic	0.9396	pathogenic	-1.249	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9998	pathogenic	-2.797	Highly Destabilizing	0.986	D	0.881	deleterious	None	None	None	None	N
L/E	0.9966	likely_pathogenic	0.9984	pathogenic	-2.46	Highly Destabilizing	0.986	D	0.879	deleterious	None	None	None	None	N
L/F	0.6654	likely_pathogenic	0.7633	pathogenic	-1.31	Destabilizing	0.986	D	0.653	neutral	None	None	None	None	N
L/G	0.9893	likely_pathogenic	0.9943	pathogenic	-2.777	Highly Destabilizing	0.986	D	0.869	deleterious	None	None	None	None	N
L/H	0.9888	likely_pathogenic	0.9941	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/I	0.3006	likely_benign	0.4331	ambiguous	-0.321	Destabilizing	0.91	D	0.644	neutral	None	None	None	None	N
L/K	0.9942	likely_pathogenic	0.9967	pathogenic	-1.477	Destabilizing	0.986	D	0.842	deleterious	None	None	None	None	N
L/M	0.366	ambiguous	0.451	ambiguous	-0.535	Destabilizing	0.58	D	0.383	neutral	D	0.65908345	None	None	N
L/N	0.9965	likely_pathogenic	0.9982	pathogenic	-2.257	Highly Destabilizing	0.986	D	0.881	deleterious	None	None	None	None	N
L/P	0.998	likely_pathogenic	0.9991	pathogenic	-0.928	Destabilizing	0.991	D	0.884	deleterious	D	0.691425704	None	None	N
L/Q	0.9815	likely_pathogenic	0.9905	pathogenic	-1.789	Destabilizing	0.991	D	0.857	deleterious	D	0.691425704	None	None	N
L/R	0.9856	likely_pathogenic	0.9917	pathogenic	-1.891	Destabilizing	0.991	D	0.865	deleterious	D	0.691425704	None	None	N
L/S	0.992	likely_pathogenic	0.9965	pathogenic	-2.73	Highly Destabilizing	0.973	D	0.835	deleterious	None	None	None	None	N
L/T	0.9762	likely_pathogenic	0.9884	pathogenic	-2.213	Highly Destabilizing	0.386	N	0.606	neutral	None	None	None	None	N
L/V	0.3577	ambiguous	0.4812	ambiguous	-0.928	Destabilizing	0.885	D	0.658	neutral	D	0.691677282	None	None	N
L/W	0.9776	likely_pathogenic	0.9887	pathogenic	-1.673	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
L/Y	0.9772	likely_pathogenic	0.9872	pathogenic	-1.439	Destabilizing	0.993	D	0.758	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.