TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7555	22888;22889;22890	chr2:178722000;178721999;178721998	chr2:179586727;179586726;179586725
N2AB	7238	21937;21938;21939	chr2:178722000;178721999;178721998	chr2:179586727;179586726;179586725
N2A	6311	19156;19157;19158	chr2:178722000;178721999;178721998	chr2:179586727;179586726;179586725
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-60
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1653
• 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
I/L	None	None	0.001	N	0.199	0.146	0.306377322295	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	0
I/V	rs747649130	-1.273	0.072	N	0.415	0.144	0.363158594168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs747649130	-1.273	0.072	N	0.415	0.144	0.363158594168	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs747649130	-1.273	0.072	N	0.415	0.144	0.363158594168	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	2.41278E-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
I/A	0.9775	likely_pathogenic	0.9828	pathogenic	-2.486	Highly Destabilizing	0.967	D	0.551	neutral	None	None	None	None	N
I/C	0.9902	likely_pathogenic	0.9922	pathogenic	-1.765	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9989	pathogenic	-2.663	Highly Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
I/E	0.9952	likely_pathogenic	0.9959	pathogenic	-2.425	Highly Destabilizing	0.994	D	0.73	prob.delet.	None	None	None	None	N
I/F	0.7055	likely_pathogenic	0.7419	pathogenic	-1.533	Destabilizing	0.939	D	0.552	neutral	N	0.502790442	None	None	N
I/G	0.9949	likely_pathogenic	0.9958	pathogenic	-3.028	Highly Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
I/H	0.993	likely_pathogenic	0.9952	pathogenic	-2.406	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
I/K	0.9857	likely_pathogenic	0.989	pathogenic	-1.964	Destabilizing	0.86	D	0.715	prob.delet.	None	None	None	None	N
I/L	0.1856	likely_benign	0.2772	benign	-0.915	Destabilizing	0.001	N	0.199	neutral	N	0.416882947	None	None	N
I/M	0.3237	likely_benign	0.3752	ambiguous	-0.845	Destabilizing	0.193	N	0.416	neutral	N	0.487559796	None	None	N
I/N	0.9799	likely_pathogenic	0.9816	pathogenic	-2.31	Highly Destabilizing	0.998	D	0.761	deleterious	D	0.527833684	None	None	N
I/P	0.9918	likely_pathogenic	0.9932	pathogenic	-1.42	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
I/Q	0.9884	likely_pathogenic	0.9921	pathogenic	-2.147	Highly Destabilizing	0.989	D	0.764	deleterious	None	None	None	None	N
I/R	0.9818	likely_pathogenic	0.9866	pathogenic	-1.753	Destabilizing	0.988	D	0.757	deleterious	None	None	None	None	N
I/S	0.9868	likely_pathogenic	0.9893	pathogenic	-3.009	Highly Destabilizing	0.994	D	0.64	neutral	N	0.518932914	None	None	N
I/T	0.9776	likely_pathogenic	0.9817	pathogenic	-2.61	Highly Destabilizing	0.87	D	0.584	neutral	N	0.51976538	None	None	N
I/V	0.2701	likely_benign	0.3053	benign	-1.42	Destabilizing	0.072	N	0.415	neutral	N	0.472376445	None	None	N
I/W	0.9877	likely_pathogenic	0.9911	pathogenic	-1.845	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
I/Y	0.9629	likely_pathogenic	0.9694	pathogenic	-1.555	Destabilizing	0.907	D	0.691	prob.neutral	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.