TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8220	24883;24884;24885	chr2:178718448;178718447;178718446	chr2:179583175;179583174;179583173
N2AB	7903	23932;23933;23934	chr2:178718448;178718447;178718446	chr2:179583175;179583174;179583173
N2A	6976	21151;21152;21153	chr2:178718448;178718447;178718446	chr2:179583175;179583174;179583173
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-67
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4562
• 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	rs763026119	-0.66	0.826	D	0.3	0.236	0.387042434762	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/A	rs763026119	-0.66	0.826	D	0.3	0.236	0.387042434762	gnomAD-4.0.0	6.36541E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.73099E-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	0.1411	likely_benign	0.1647	benign	-0.561	Destabilizing	0.826	D	0.3	neutral	D	0.53675321	None	None	I
T/C	0.6405	likely_pathogenic	0.7267	pathogenic	-0.256	Destabilizing	0.1	N	0.228	neutral	None	None	None	None	I
T/D	0.6408	likely_pathogenic	0.6692	pathogenic	0.091	Stabilizing	0.969	D	0.38	neutral	None	None	None	None	I
T/E	0.4917	ambiguous	0.5323	ambiguous	0.031	Stabilizing	0.939	D	0.351	neutral	None	None	None	None	I
T/F	0.308	likely_benign	0.3852	ambiguous	-0.928	Destabilizing	0.997	D	0.513	neutral	None	None	None	None	I
T/G	0.4617	ambiguous	0.485	ambiguous	-0.732	Destabilizing	0.969	D	0.433	neutral	None	None	None	None	I
T/H	0.3276	likely_benign	0.3729	ambiguous	-1.087	Destabilizing	0.997	D	0.477	neutral	None	None	None	None	I
T/I	0.191	likely_benign	0.2973	benign	-0.218	Destabilizing	0.988	D	0.423	neutral	N	0.50437422	None	None	I
T/K	0.3201	likely_benign	0.3817	ambiguous	-0.452	Destabilizing	0.17	N	0.191	neutral	None	None	None	None	I
T/L	0.1509	likely_benign	0.1941	benign	-0.218	Destabilizing	0.939	D	0.37	neutral	None	None	None	None	I
T/M	0.1239	likely_benign	0.1491	benign	0.117	Stabilizing	0.997	D	0.411	neutral	None	None	None	None	I
T/N	0.2101	likely_benign	0.2422	benign	-0.231	Destabilizing	0.959	D	0.32	neutral	N	0.500749299	None	None	I
T/P	0.6301	likely_pathogenic	0.6569	pathogenic	-0.302	Destabilizing	0.035	N	0.204	neutral	D	0.530970328	None	None	I
T/Q	0.3151	likely_benign	0.3597	ambiguous	-0.492	Destabilizing	0.982	D	0.428	neutral	None	None	None	None	I
T/R	0.2282	likely_benign	0.2842	benign	-0.18	Destabilizing	0.046	N	0.233	neutral	None	None	None	None	I
T/S	0.1731	likely_benign	0.1789	benign	-0.487	Destabilizing	0.826	D	0.336	neutral	D	0.525189422	None	None	I
T/V	0.1738	likely_benign	0.2488	benign	-0.302	Destabilizing	0.939	D	0.273	neutral	None	None	None	None	I
T/W	0.6887	likely_pathogenic	0.7372	pathogenic	-0.871	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	I
T/Y	0.3769	ambiguous	0.4433	ambiguous	-0.617	Destabilizing	0.997	D	0.513	neutral	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.