TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16286	49081;49082;49083	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
N2AB	14645	44158;44159;44160	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
N2A	13718	41377;41378;41379	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
N2B	7221	21886;21887;21888	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
Novex-1	7346	22261;22262;22263	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
Novex-2	7413	22462;22463;22464	chr2:178614658;178614657;178614656	chr2:179479385;179479384;179479383
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-110
• Domain position: 25
• Structural Position: 42
• Q(SASA): 0.54
• 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
P/T	rs1033904978	None	1.0	D	0.75	0.764	0.773923737282	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	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
P/A	0.9719	likely_pathogenic	0.9717	pathogenic	-0.54	Destabilizing	1.0	D	0.751	deleterious	D	0.7934190249999999	None	None	I
P/C	0.9978	likely_pathogenic	0.9976	pathogenic	-0.414	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
P/D	0.9908	likely_pathogenic	0.9901	pathogenic	-0.628	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/E	0.99	likely_pathogenic	0.9893	pathogenic	-0.752	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/F	0.9986	likely_pathogenic	0.9987	pathogenic	-0.835	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/G	0.9874	likely_pathogenic	0.9869	pathogenic	-0.672	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/H	0.9914	likely_pathogenic	0.9904	pathogenic	-0.354	Destabilizing	1.0	D	0.793	deleterious	D	0.809540418	None	None	I
P/I	0.9888	likely_pathogenic	0.9889	pathogenic	-0.338	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/K	0.9875	likely_pathogenic	0.9868	pathogenic	-0.542	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/L	0.9701	likely_pathogenic	0.9689	pathogenic	-0.338	Destabilizing	1.0	D	0.767	deleterious	D	0.843279989	None	None	I
P/M	0.9908	likely_pathogenic	0.991	pathogenic	-0.282	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
P/N	0.9909	likely_pathogenic	0.9914	pathogenic	-0.145	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
P/Q	0.9899	likely_pathogenic	0.9897	pathogenic	-0.432	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/R	0.9803	likely_pathogenic	0.9787	pathogenic	0.016	Stabilizing	1.0	D	0.79	deleterious	D	0.827312724	None	None	I
P/S	0.9926	likely_pathogenic	0.9929	pathogenic	-0.428	Destabilizing	1.0	D	0.752	deleterious	D	0.792231392	None	None	I
P/T	0.9746	likely_pathogenic	0.9728	pathogenic	-0.462	Destabilizing	1.0	D	0.75	deleterious	D	0.827312724	None	None	I
P/V	0.9753	likely_pathogenic	0.9759	pathogenic	-0.371	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/W	0.9989	likely_pathogenic	0.9989	pathogenic	-0.932	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
P/Y	0.9971	likely_pathogenic	0.9971	pathogenic	-0.638	Destabilizing	1.0	D	0.817	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.