TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31298	94117;94118;94119	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
N2AB	29657	89194;89195;89196	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
N2A	28730	86413;86414;86415	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
N2B	22233	66922;66923;66924	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
Novex-1	22358	67297;67298;67299	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
Novex-2	22425	67498;67499;67500	chr2:178547734;178547733;178547732	chr2:179412461;179412460;179412459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-151
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.2769
• 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	rs1697809647	None	0.999	N	0.539	0.47	0.468834750356	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.1265	likely_benign	0.1498	benign	-0.749	Destabilizing	0.999	D	0.539	neutral	N	0.487039591	None	None	N
T/C	0.5422	ambiguous	0.5833	pathogenic	-0.41	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/D	0.4406	ambiguous	0.502	ambiguous	0.647	Stabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
T/E	0.3741	ambiguous	0.4105	ambiguous	0.687	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
T/F	0.4534	ambiguous	0.5224	ambiguous	-0.917	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
T/G	0.3591	ambiguous	0.4266	ambiguous	-1.003	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/H	0.3325	likely_benign	0.3768	ambiguous	-1.052	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/I	0.2537	likely_benign	0.2883	benign	-0.162	Destabilizing	1.0	D	0.867	deleterious	D	0.528752589	None	None	N
T/K	0.2956	likely_benign	0.327	benign	-0.127	Destabilizing	1.0	D	0.864	deleterious	N	0.482862797	None	None	N
T/L	0.1857	likely_benign	0.2179	benign	-0.162	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
T/M	0.1145	likely_benign	0.125	benign	-0.189	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/N	0.1318	likely_benign	0.1489	benign	-0.244	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/P	0.2813	likely_benign	0.3472	ambiguous	-0.326	Destabilizing	1.0	D	0.854	deleterious	N	0.503702268	None	None	N
T/Q	0.2724	likely_benign	0.3048	benign	-0.24	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
T/R	0.2694	likely_benign	0.3019	benign	-0.054	Destabilizing	1.0	D	0.863	deleterious	N	0.519266315	None	None	N
T/S	0.1308	likely_benign	0.143	benign	-0.647	Destabilizing	0.999	D	0.522	neutral	N	0.450097018	None	None	N
T/V	0.1948	likely_benign	0.2107	benign	-0.326	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
T/W	0.7779	likely_pathogenic	0.8226	pathogenic	-0.884	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
T/Y	0.3914	ambiguous	0.4375	ambiguous	-0.582	Destabilizing	1.0	D	0.864	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.