TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18364	55315;55316;55317	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
N2AB	16723	50392;50393;50394	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
N2A	15796	47611;47612;47613	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
N2B	9299	28120;28121;28122	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
Novex-1	9424	28495;28496;28497	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
Novex-2	9491	28696;28697;28698	chr2:178602312;178602311;178602310	chr2:179467039;179467038;179467037
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: Fn3-21
• Domain position: 93
• Structural Position: 124
• Q(SASA): 0.2587
• 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/A	rs1467489292	None	0.997	N	0.677	0.211	0.335910606209	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs1467489292	None	0.997	N	0.677	0.211	0.335910606209	gnomAD-4.0.0	6.57748E-06	None	None	None	None	N	None	2.41301E-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
T/A	0.1497	likely_benign	0.1515	benign	-1.133	Destabilizing	0.997	D	0.677	prob.neutral	N	0.508486387	None	None	N
T/C	0.5169	ambiguous	0.5708	pathogenic	-0.628	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
T/D	0.6606	likely_pathogenic	0.6832	pathogenic	-0.485	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
T/E	0.6178	likely_pathogenic	0.6298	pathogenic	-0.375	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
T/F	0.6179	likely_pathogenic	0.6538	pathogenic	-0.898	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
T/G	0.3584	ambiguous	0.3879	ambiguous	-1.497	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
T/H	0.5656	likely_pathogenic	0.6041	pathogenic	-1.575	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
T/I	0.4526	ambiguous	0.4647	ambiguous	-0.212	Destabilizing	0.999	D	0.842	deleterious	D	0.527421651	None	None	N
T/K	0.5014	ambiguous	0.5054	ambiguous	-0.591	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
T/L	0.2571	likely_benign	0.2777	benign	-0.212	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
T/M	0.2248	likely_benign	0.2389	benign	-0.054	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/N	0.3386	likely_benign	0.358	ambiguous	-0.869	Destabilizing	0.999	D	0.789	deleterious	N	0.516331886	None	None	N
T/P	0.2458	likely_benign	0.2899	benign	-0.486	Destabilizing	0.999	D	0.826	deleterious	N	0.480590496	None	None	N
T/Q	0.5134	ambiguous	0.5335	ambiguous	-0.835	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
T/R	0.4438	ambiguous	0.464	ambiguous	-0.561	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
T/S	0.1592	likely_benign	0.1687	benign	-1.231	Destabilizing	0.997	D	0.691	prob.delet.	N	0.409551543	None	None	N
T/V	0.2873	likely_benign	0.2922	benign	-0.486	Destabilizing	0.998	D	0.732	deleterious	None	None	None	None	N
T/W	0.8353	likely_pathogenic	0.8698	pathogenic	-0.86	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
T/Y	0.6775	likely_pathogenic	0.707	pathogenic	-0.584	Destabilizing	1.0	D	0.874	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.