TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30997	93214;93215;93216	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
N2AB	29356	88291;88292;88293	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
N2A	28429	85510;85511;85512	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
N2B	21932	66019;66020;66021	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
Novex-1	22057	66394;66395;66396	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
Novex-2	22124	66595;66596;66597	chr2:178548637;178548636;178548635	chr2:179413364;179413363;179413362
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-150
• Domain position: 71
• Structural Position: 157
• Q(SASA): 0.2157
• 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	rs981213729	-0.298	0.782	D	0.734	0.315	0.491387584038	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs981213729	-0.298	0.782	D	0.734	0.315	0.491387584038	gnomAD-4.0.0	6.15764E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29613E-06	2.31863E-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	0.086	likely_benign	0.0891	benign	-0.843	Destabilizing	0.174	N	0.515	neutral	N	0.509761747	None	None	N
T/C	0.3023	likely_benign	0.3035	benign	-0.767	Destabilizing	0.973	D	0.719	prob.delet.	None	None	None	None	N
T/D	0.465	ambiguous	0.481	ambiguous	-0.849	Destabilizing	0.575	D	0.695	prob.neutral	None	None	None	None	N
T/E	0.311	likely_benign	0.34	ambiguous	-0.843	Destabilizing	0.404	N	0.698	prob.neutral	None	None	None	None	N
T/F	0.2031	likely_benign	0.2121	benign	-1.072	Destabilizing	0.906	D	0.793	deleterious	None	None	None	None	N
T/G	0.2933	likely_benign	0.3053	benign	-1.073	Destabilizing	0.404	N	0.687	prob.neutral	None	None	None	None	N
T/H	0.1704	likely_benign	0.1809	benign	-1.435	Destabilizing	0.973	D	0.776	deleterious	None	None	None	None	N
T/I	0.1301	likely_benign	0.1382	benign	-0.321	Destabilizing	0.782	D	0.734	prob.delet.	D	0.532347468	None	None	N
T/K	0.1604	likely_benign	0.1764	benign	-0.68	Destabilizing	0.404	N	0.697	prob.neutral	None	None	None	None	N
T/L	0.0934	likely_benign	0.0968	benign	-0.321	Destabilizing	0.575	D	0.667	neutral	None	None	None	None	N
T/M	0.0802	likely_benign	0.0804	benign	0.002	Stabilizing	0.991	D	0.731	prob.delet.	None	None	None	None	N
T/N	0.145	likely_benign	0.1529	benign	-0.753	Destabilizing	0.338	N	0.625	neutral	N	0.501621446	None	None	N
T/P	0.7535	likely_pathogenic	0.78	pathogenic	-0.465	Destabilizing	0.879	D	0.732	prob.delet.	D	0.529386939	None	None	N
T/Q	0.1805	likely_benign	0.188	benign	-1.029	Destabilizing	0.826	D	0.763	deleterious	None	None	None	None	N
T/R	0.1329	likely_benign	0.1465	benign	-0.429	Destabilizing	0.826	D	0.751	deleterious	None	None	None	None	N
T/S	0.1109	likely_benign	0.1141	benign	-0.967	Destabilizing	0.001	N	0.323	neutral	N	0.516647297	None	None	N
T/V	0.1179	likely_benign	0.1222	benign	-0.465	Destabilizing	0.575	D	0.599	neutral	None	None	None	None	N
T/W	0.4896	ambiguous	0.5198	ambiguous	-1.002	Destabilizing	0.991	D	0.779	deleterious	None	None	None	None	N
T/Y	0.2357	likely_benign	0.2555	benign	-0.715	Destabilizing	0.906	D	0.799	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.