TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29533	88822;88823;88824	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
N2AB	27892	83899;83900;83901	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
N2A	26965	81118;81119;81120	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
N2B	20468	61627;61628;61629	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
Novex-1	20593	62002;62003;62004	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
Novex-2	20660	62203;62204;62205	chr2:178554750;178554749;178554748	chr2:179419477;179419476;179419475
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: Fn3-103
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.0495
• 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
K/N	None	None	0.999	N	0.807	0.305	0.156986980423	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.534	ambiguous	0.5441	ambiguous	-0.179	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	I
K/C	0.7037	likely_pathogenic	0.7149	pathogenic	-0.309	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
K/D	0.9104	likely_pathogenic	0.9197	pathogenic	0.21	Stabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
K/E	0.3941	ambiguous	0.4143	ambiguous	0.235	Stabilizing	0.997	D	0.787	deleterious	N	0.483862455	None	None	I
K/F	0.8912	likely_pathogenic	0.8972	pathogenic	-0.272	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
K/G	0.784	likely_pathogenic	0.7996	pathogenic	-0.423	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
K/H	0.4982	ambiguous	0.5122	ambiguous	-0.737	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
K/I	0.332	likely_benign	0.3389	benign	0.395	Stabilizing	0.999	D	0.844	deleterious	N	0.465251221	None	None	I
K/L	0.5196	ambiguous	0.5222	ambiguous	0.395	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
K/M	0.3207	likely_benign	0.327	benign	0.304	Stabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
K/N	0.7252	likely_pathogenic	0.7451	pathogenic	0.154	Stabilizing	0.999	D	0.807	deleterious	N	0.484369434	None	None	I
K/P	0.8527	likely_pathogenic	0.8682	pathogenic	0.233	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
K/Q	0.2088	likely_benign	0.218	benign	-0.069	Destabilizing	0.999	D	0.831	deleterious	N	0.484369434	None	None	I
K/R	0.087	likely_benign	0.0881	benign	-0.093	Destabilizing	0.997	D	0.688	prob.delet.	N	0.433139613	None	None	I
K/S	0.6429	likely_pathogenic	0.6614	pathogenic	-0.468	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	I
K/T	0.2211	likely_benign	0.2296	benign	-0.278	Destabilizing	0.999	D	0.798	deleterious	N	0.455211588	None	None	I
K/V	0.295	likely_benign	0.305	benign	0.233	Stabilizing	0.999	D	0.782	deleterious	None	None	None	None	I
K/W	0.9262	likely_pathogenic	0.9301	pathogenic	-0.176	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
K/Y	0.8166	likely_pathogenic	0.8248	pathogenic	0.156	Stabilizing	1.0	D	0.851	deleterious	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.