TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18134	54625;54626;54627	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
N2AB	16493	49702;49703;49704	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
N2A	15566	46921;46922;46923	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
N2B	9069	27430;27431;27432	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
Novex-1	9194	27805;27806;27807	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
Novex-2	9261	28006;28007;28008	chr2:178604287;178604286;178604285	chr2:179469014;179469013;179469012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-19
• Domain position: 70
• Structural Position: 100
• Q(SASA): 0.6177
• 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
N/K	rs1020792831	None	0.997	N	0.615	0.308	0.219573609325	gnomAD-4.0.0	2.25945E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	5.77367E-04	0	0	0
N/S	rs971483896	None	0.978	N	0.548	0.244	0.232513804876	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
N/S	rs971483896	None	0.978	N	0.548	0.244	0.232513804876	gnomAD-4.0.0	1.96056E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.51599E-05	1.55366E-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
N/A	0.1975	likely_benign	0.2086	benign	-0.307	Destabilizing	0.967	D	0.623	neutral	None	None	None	None	N
N/C	0.3006	likely_benign	0.3086	benign	0.3	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/D	0.1227	likely_benign	0.1461	benign	0.109	Stabilizing	0.989	D	0.585	neutral	N	0.460990723	None	None	N
N/E	0.3164	likely_benign	0.3891	ambiguous	0.095	Stabilizing	0.997	D	0.615	neutral	None	None	None	None	N
N/F	0.5042	ambiguous	0.5136	ambiguous	-0.518	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
N/G	0.1498	likely_benign	0.16	benign	-0.516	Destabilizing	0.071	N	0.311	neutral	None	None	None	None	N
N/H	0.0981	likely_benign	0.1026	benign	-0.481	Destabilizing	0.999	D	0.615	neutral	N	0.476325535	None	None	N
N/I	0.5116	ambiguous	0.5309	ambiguous	0.164	Stabilizing	0.999	D	0.764	deleterious	N	0.485398116	None	None	N
N/K	0.236	likely_benign	0.2878	benign	0.01	Stabilizing	0.997	D	0.615	neutral	N	0.471111716	None	None	N
N/L	0.3029	likely_benign	0.3099	benign	0.164	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
N/M	0.3975	ambiguous	0.4027	ambiguous	0.406	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
N/P	0.8391	likely_pathogenic	0.8559	pathogenic	0.035	Stabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
N/Q	0.2419	likely_benign	0.2771	benign	-0.414	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
N/R	0.2703	likely_benign	0.324	benign	0.045	Stabilizing	0.999	D	0.615	neutral	None	None	None	None	N
N/S	0.0806	likely_benign	0.0835	benign	-0.235	Destabilizing	0.978	D	0.548	neutral	N	0.470418283	None	None	N
N/T	0.172	likely_benign	0.1848	benign	-0.1	Destabilizing	0.989	D	0.618	neutral	N	0.499010394	None	None	N
N/V	0.4068	ambiguous	0.4355	ambiguous	0.035	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
N/W	0.716	likely_pathogenic	0.7419	pathogenic	-0.471	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/Y	0.1642	likely_benign	0.1672	benign	-0.224	Destabilizing	0.999	D	0.726	prob.delet.	N	0.437711219	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.