TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8512	25759;25760;25761	chr2:178717200;178717199;178717198	chr2:179581927;179581926;179581925
N2AB	8195	24808;24809;24810	chr2:178717200;178717199;178717198	chr2:179581927;179581926;179581925
N2A	7268	22027;22028;22029	chr2:178717200;178717199;178717198	chr2:179581927;179581926;179581925
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-70
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.177
• 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	rs764620561	0.193	0.995	N	0.677	0.446	0.452450644169	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	7.81E-06	0
T/I	rs764620561	0.193	0.995	N	0.677	0.446	0.452450644169	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs764620561	0.193	0.995	N	0.677	0.446	0.452450644169	gnomAD-4.0.0	3.71849E-06	None	None	None	None	N	None	0	1.66711E-05	None	0	0	None	0	0	2.54308E-06	0	3.20338E-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
T/A	0.0869	likely_benign	0.0865	benign	-1.072	Destabilizing	0.308	N	0.478	neutral	N	0.509358752	None	None	N
T/C	0.3922	ambiguous	0.412	ambiguous	-0.835	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
T/D	0.447	ambiguous	0.4649	ambiguous	-1.463	Destabilizing	0.898	D	0.631	neutral	None	None	None	None	N
T/E	0.3019	likely_benign	0.3164	benign	-1.317	Destabilizing	0.967	D	0.607	neutral	None	None	None	None	N
T/F	0.1499	likely_benign	0.1594	benign	-0.872	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
T/G	0.2995	likely_benign	0.3024	benign	-1.459	Destabilizing	0.974	D	0.622	neutral	None	None	None	None	N
T/H	0.1991	likely_benign	0.2068	benign	-1.718	Destabilizing	0.114	N	0.499	neutral	None	None	None	None	N
T/I	0.1161	likely_benign	0.1233	benign	-0.078	Destabilizing	0.995	D	0.677	prob.neutral	N	0.496392242	None	None	N
T/K	0.2632	likely_benign	0.2736	benign	-0.727	Destabilizing	0.954	D	0.607	neutral	None	None	None	None	N
T/L	0.0881	likely_benign	0.0938	benign	-0.078	Destabilizing	0.976	D	0.613	neutral	None	None	None	None	N
T/M	0.0801	likely_benign	0.0831	benign	0.09	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	N
T/N	0.1352	likely_benign	0.136	benign	-1.289	Destabilizing	0.869	D	0.605	neutral	N	0.501528703	None	None	N
T/P	0.6936	likely_pathogenic	0.6952	pathogenic	-0.376	Destabilizing	0.979	D	0.679	prob.neutral	N	0.50538779	None	None	N
T/Q	0.2138	likely_benign	0.2218	benign	-1.188	Destabilizing	0.985	D	0.675	prob.neutral	None	None	None	None	N
T/R	0.198	likely_benign	0.2078	benign	-0.802	Destabilizing	0.256	N	0.494	neutral	None	None	None	None	N
T/S	0.0973	likely_benign	0.0969	benign	-1.471	Destabilizing	0.012	N	0.241	neutral	N	0.443613763	None	None	N
T/V	0.1009	likely_benign	0.1063	benign	-0.376	Destabilizing	0.967	D	0.624	neutral	None	None	None	None	N
T/W	0.4883	ambiguous	0.5121	ambiguous	-0.986	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
T/Y	0.195	likely_benign	0.2053	benign	-0.634	Destabilizing	0.997	D	0.655	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.