TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22220	66883;66884;66885	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
N2AB	20579	61960;61961;61962	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
N2A	19652	59179;59180;59181	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
N2B	13155	39688;39689;39690	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
Novex-1	13280	40063;40064;40065	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
Novex-2	13347	40264;40265;40266	chr2:178581610;178581609;178581608	chr2:179446337;179446336;179446335
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: Fn3-49
• Domain position: 65
• Structural Position: 94
• Q(SASA): 0.5178
• 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
T/I	None	None	1.0	N	0.807	0.431	0.495706241231	gnomAD-4.0.0	1.36926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31949E-05	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	0.0971	likely_benign	0.0899	benign	-0.474	Destabilizing	0.999	D	0.505	neutral	N	0.507477948	None	None	N
T/C	0.3782	ambiguous	0.3453	ambiguous	-0.342	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/D	0.461	ambiguous	0.4148	ambiguous	0.404	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/E	0.3099	likely_benign	0.2741	benign	0.331	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/F	0.3801	ambiguous	0.3307	benign	-1.005	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/G	0.2362	likely_benign	0.2287	benign	-0.592	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/H	0.2345	likely_benign	0.2122	benign	-0.877	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
T/I	0.2267	likely_benign	0.2028	benign	-0.285	Destabilizing	1.0	D	0.807	deleterious	N	0.475767012	None	None	N
T/K	0.1341	likely_benign	0.1202	benign	-0.272	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/L	0.1346	likely_benign	0.1158	benign	-0.285	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
T/M	0.1196	likely_benign	0.1062	benign	-0.1	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
T/N	0.1433	likely_benign	0.1319	benign	-0.103	Destabilizing	1.0	D	0.687	prob.neutral	N	0.470687676	None	None	N
T/P	0.1126	likely_benign	0.0985	benign	-0.32	Destabilizing	1.0	D	0.811	deleterious	N	0.505784437	None	None	N
T/Q	0.1898	likely_benign	0.1724	benign	-0.316	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/R	0.1447	likely_benign	0.1277	benign	-0.039	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
T/S	0.1199	likely_benign	0.1107	benign	-0.366	Destabilizing	0.999	D	0.496	neutral	N	0.490486911	None	None	N
T/V	0.1666	likely_benign	0.1545	benign	-0.32	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
T/W	0.6876	likely_pathogenic	0.634	pathogenic	-0.981	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/Y	0.376	ambiguous	0.3303	benign	-0.696	Destabilizing	1.0	D	0.809	deleterious	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.