TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2904	8935;8936;8937	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
N2AB	2904	8935;8936;8937	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
N2A	2904	8935;8936;8937	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
N2B	2858	8797;8798;8799	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
Novex-1	2858	8797;8798;8799	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
Novex-2	2858	8797;8798;8799	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596
Novex-3	2904	8935;8936;8937	chr2:178769871;178769870;178769869	chr2:179634598;179634597;179634596

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-19
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1795
• 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
E/K	rs794729583	None	0.999	D	0.555	0.583	0.499858025796	gnomAD-4.0.0	6.15665E-06	None	None	None	None	N	None	0	0	None	0	2.51965E-05	None	0	0	0	1.15931E-05	1.15902E-04

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
E/A	0.6912	likely_pathogenic	0.5541	ambiguous	-1.094	Destabilizing	0.999	D	0.663	neutral	D	0.627719197	None	None	N
E/C	0.9883	likely_pathogenic	0.9836	pathogenic	-0.738	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.8755	likely_pathogenic	0.8256	pathogenic	-1.48	Destabilizing	0.999	D	0.453	neutral	D	0.647184484	None	None	N
E/F	0.9893	likely_pathogenic	0.9821	pathogenic	-0.915	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/G	0.8895	likely_pathogenic	0.8112	pathogenic	-1.461	Destabilizing	1.0	D	0.732	prob.delet.	D	0.604227927	None	None	N
E/H	0.9619	likely_pathogenic	0.9432	pathogenic	-1.205	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.8701	likely_pathogenic	0.8142	pathogenic	-0.083	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/K	0.7948	likely_pathogenic	0.6778	pathogenic	-1.123	Destabilizing	0.999	D	0.555	neutral	D	0.540795114	None	None	N
E/L	0.9413	likely_pathogenic	0.8954	pathogenic	-0.083	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/M	0.899	likely_pathogenic	0.837	pathogenic	0.492	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/N	0.9397	likely_pathogenic	0.9087	pathogenic	-1.42	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/P	0.998	likely_pathogenic	0.9972	pathogenic	-0.4	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.5693	likely_pathogenic	0.4485	ambiguous	-1.272	Destabilizing	1.0	D	0.589	neutral	N	0.502365181	None	None	N
E/R	0.8907	likely_pathogenic	0.8223	pathogenic	-0.953	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/S	0.8125	likely_pathogenic	0.7169	pathogenic	-1.871	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
E/T	0.7992	likely_pathogenic	0.7273	pathogenic	-1.557	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/V	0.7072	likely_pathogenic	0.6284	pathogenic	-0.4	Destabilizing	1.0	D	0.771	deleterious	D	0.599142732	None	None	N
E/W	0.9977	likely_pathogenic	0.9963	pathogenic	-0.859	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9865	likely_pathogenic	0.9781	pathogenic	-0.707	Destabilizing	1.0	D	0.773	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.