TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28511	85756;85757;85758	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
N2AB	26870	80833;80834;80835	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
N2A	25943	78052;78053;78054	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
N2B	19446	58561;58562;58563	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
Novex-1	19571	58936;58937;58938	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
Novex-2	19638	59137;59138;59139	chr2:178560601;178560600;178560599	chr2:179425328;179425327;179425326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-95
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4065
• 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
K/N	None	None	1.0	N	0.725	0.32	0.193865811164	gnomAD-4.0.0	1.20032E-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
K/A	0.5208	ambiguous	0.5197	ambiguous	-0.067	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
K/C	0.7417	likely_pathogenic	0.7793	pathogenic	-0.134	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/D	0.7437	likely_pathogenic	0.7426	pathogenic	0.059	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/E	0.3226	likely_benign	0.3008	benign	0.074	Stabilizing	0.999	D	0.602	neutral	N	0.519710953	None	None	N
K/F	0.8339	likely_pathogenic	0.8462	pathogenic	-0.216	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/G	0.6937	likely_pathogenic	0.6954	pathogenic	-0.298	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/H	0.3422	ambiguous	0.3578	ambiguous	-0.646	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
K/I	0.3991	ambiguous	0.3982	ambiguous	0.47	Stabilizing	1.0	D	0.845	deleterious	N	0.478761844	None	None	N
K/L	0.4833	ambiguous	0.4697	ambiguous	0.47	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/M	0.3092	likely_benign	0.2939	benign	0.376	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/N	0.5962	likely_pathogenic	0.5885	pathogenic	0.219	Stabilizing	1.0	D	0.725	prob.delet.	N	0.48925476	None	None	N
K/P	0.8021	likely_pathogenic	0.809	pathogenic	0.32	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/Q	0.2009	likely_benign	0.1915	benign	0.017	Stabilizing	1.0	D	0.695	prob.neutral	N	0.516190645	None	None	N
K/R	0.0847	likely_benign	0.0876	benign	-0.081	Destabilizing	0.999	D	0.566	neutral	N	0.51465185	None	None	N
K/S	0.5575	ambiguous	0.5606	ambiguous	-0.311	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/T	0.2191	likely_benign	0.2048	benign	-0.137	Destabilizing	1.0	D	0.799	deleterious	N	0.437628287	None	None	N
K/V	0.3644	ambiguous	0.3628	ambiguous	0.32	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/W	0.7809	likely_pathogenic	0.8014	pathogenic	-0.185	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/Y	0.6983	likely_pathogenic	0.7241	pathogenic	0.16	Stabilizing	1.0	D	0.818	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.