TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18189	54790;54791;54792	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
N2AB	16548	49867;49868;49869	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
N2A	15621	47086;47087;47088	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
N2B	9124	27595;27596;27597	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
Novex-1	9249	27970;27971;27972	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
Novex-2	9316	28171;28172;28173	chr2:178604122;178604121;178604120	chr2:179468849;179468848;179468847
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: Fn3-20
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4735
• 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	rs2054184050	None	1.0	N	0.874	0.443	0.509168631294	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
P/T	rs2054184050	None	1.0	N	0.874	0.443	0.509168631294	gnomAD-4.0.0	2.03023E-06	None	None	None	None	I	None	0	6.15764E-05	None	0	0	None	0	0	0	0	3.40298E-05

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	0.0971	likely_benign	0.0857	benign	-1.677	Destabilizing	1.0	D	0.816	deleterious	N	0.497493028	None	None	I
P/C	0.7301	likely_pathogenic	0.6824	pathogenic	-1.244	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/D	0.7438	likely_pathogenic	0.7177	pathogenic	-1.616	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
P/E	0.4138	ambiguous	0.3695	ambiguous	-1.502	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
P/F	0.7232	likely_pathogenic	0.6363	pathogenic	-1.09	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
P/G	0.5014	ambiguous	0.4664	ambiguous	-2.085	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
P/H	0.4069	ambiguous	0.3529	ambiguous	-1.475	Destabilizing	1.0	D	0.861	deleterious	N	0.497090952	None	None	I
P/I	0.4951	ambiguous	0.4309	ambiguous	-0.603	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
P/K	0.5317	ambiguous	0.479	ambiguous	-1.408	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
P/L	0.207	likely_benign	0.1528	benign	-0.603	Destabilizing	1.0	D	0.885	deleterious	N	0.504319427	None	None	I
P/M	0.4425	ambiguous	0.385	ambiguous	-0.642	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/N	0.5807	likely_pathogenic	0.5765	pathogenic	-1.455	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
P/Q	0.2538	likely_benign	0.2152	benign	-1.451	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/R	0.3814	ambiguous	0.3192	benign	-1.054	Destabilizing	1.0	D	0.889	deleterious	N	0.502170916	None	None	I
P/S	0.2168	likely_benign	0.1934	benign	-2.035	Highly Destabilizing	1.0	D	0.873	deleterious	N	0.476162313	None	None	I
P/T	0.2392	likely_benign	0.2047	benign	-1.781	Destabilizing	1.0	D	0.874	deleterious	N	0.489747118	None	None	I
P/V	0.3142	likely_benign	0.2706	benign	-0.93	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/W	0.8829	likely_pathogenic	0.8382	pathogenic	-1.336	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
P/Y	0.6723	likely_pathogenic	0.6071	pathogenic	-1.008	Destabilizing	1.0	D	0.885	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.