TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6132	18619;18620;18621	chr2:178729859;178729858;178729857	chr2:179594586;179594585;179594584
N2AB	5815	17668;17669;17670	chr2:178729859;178729858;178729857	chr2:179594586;179594585;179594584
N2A	4888	14887;14888;14889	chr2:178729859;178729858;178729857	chr2:179594586;179594585;179594584
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-45
• Domain position: 28
• Structural Position: 41
• Q(SASA): 0.6178
• 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
T/A	None	None	0.999	N	0.58	0.29	0.382925413656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.148	likely_benign	0.1604	benign	-0.154	Destabilizing	0.999	D	0.58	neutral	N	0.519012811	None	None	I
T/C	0.6931	likely_pathogenic	0.7258	pathogenic	-0.296	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
T/D	0.4484	ambiguous	0.4786	ambiguous	0.017	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/E	0.3849	ambiguous	0.4137	ambiguous	-0.071	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
T/F	0.2258	likely_benign	0.2645	benign	-0.741	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
T/G	0.4326	ambiguous	0.4856	ambiguous	-0.242	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
T/H	0.2916	likely_benign	0.3182	benign	-0.412	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
T/I	0.2431	likely_benign	0.268	benign	-0.046	Destabilizing	1.0	D	0.77	deleterious	N	0.506393018	None	None	I
T/K	0.2182	likely_benign	0.229	benign	-0.312	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
T/L	0.1476	likely_benign	0.1645	benign	-0.046	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
T/M	0.1079	likely_benign	0.1144	benign	-0.069	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
T/N	0.1239	likely_benign	0.1315	benign	-0.074	Destabilizing	1.0	D	0.818	deleterious	N	0.451134381	None	None	I
T/P	0.4965	ambiguous	0.4991	ambiguous	-0.056	Destabilizing	1.0	D	0.773	deleterious	N	0.508142359	None	None	I
T/Q	0.2663	likely_benign	0.2845	benign	-0.296	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
T/R	0.2021	likely_benign	0.2152	benign	0.003	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
T/S	0.1128	likely_benign	0.1234	benign	-0.241	Destabilizing	0.999	D	0.616	neutral	N	0.411903989	None	None	I
T/V	0.229	likely_benign	0.2468	benign	-0.056	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
T/W	0.6129	likely_pathogenic	0.6589	pathogenic	-0.815	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
T/Y	0.2823	likely_benign	0.3072	benign	-0.501	Destabilizing	1.0	D	0.807	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.