TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2322	7189;7190;7191	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
N2AB	2322	7189;7190;7191	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
N2A	2322	7189;7190;7191	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
N2B	2276	7051;7052;7053	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
Novex-1	2276	7051;7052;7053	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
Novex-2	2276	7051;7052;7053	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025
Novex-3	2322	7189;7190;7191	chr2:178774300;178774299;178774298	chr2:179639027;179639026;179639025

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-12
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.1647
• 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/I	rs1283394684	0.228	0.006	N	0.522	0.343	0.438806408302	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
N/I	rs1283394684	0.228	0.006	N	0.522	0.343	0.438806408302	gnomAD-4.0.0	1.59057E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85675E-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
N/A	0.1708	likely_benign	0.1762	benign	-0.97	Destabilizing	0.176	N	0.487	neutral	None	None	None	None	N
N/C	0.2155	likely_benign	0.2242	benign	-0.452	Destabilizing	0.981	D	0.588	neutral	None	None	None	None	N
N/D	0.2477	likely_benign	0.2556	benign	-1.836	Destabilizing	0.425	N	0.415	neutral	N	0.477922482	None	None	N
N/E	0.4239	ambiguous	0.4457	ambiguous	-1.61	Destabilizing	0.495	N	0.403	neutral	None	None	None	None	N
N/F	0.2839	likely_benign	0.2953	benign	-0.612	Destabilizing	0.893	D	0.62	neutral	None	None	None	None	N
N/G	0.2898	likely_benign	0.2968	benign	-1.363	Destabilizing	0.495	N	0.397	neutral	None	None	None	None	N
N/H	0.1073	likely_benign	0.1086	benign	-1.026	Destabilizing	0.975	D	0.559	neutral	N	0.442889034	None	None	N
N/I	0.0777	likely_benign	0.0793	benign	0.069	Stabilizing	0.006	N	0.522	neutral	N	0.395043653	None	None	N
N/K	0.2892	likely_benign	0.3145	benign	-0.166	Destabilizing	0.425	N	0.408	neutral	N	0.288038055	None	None	N
N/L	0.1312	likely_benign	0.1384	benign	0.069	Stabilizing	0.329	N	0.509	neutral	None	None	None	None	N
N/M	0.1645	likely_benign	0.1687	benign	0.265	Stabilizing	0.893	D	0.563	neutral	None	None	None	None	N
N/P	0.9303	likely_pathogenic	0.9366	pathogenic	-0.25	Destabilizing	0.828	D	0.577	neutral	None	None	None	None	N
N/Q	0.2953	likely_benign	0.3126	benign	-0.824	Destabilizing	0.828	D	0.522	neutral	None	None	None	None	N
N/R	0.3407	ambiguous	0.3738	ambiguous	-0.396	Destabilizing	0.828	D	0.48	neutral	None	None	None	None	N
N/S	0.0835	likely_benign	0.0838	benign	-1.129	Destabilizing	0.029	N	0.231	neutral	N	0.305676661	None	None	N
N/T	0.0811	likely_benign	0.0847	benign	-0.717	Destabilizing	0.003	N	0.171	neutral	N	0.36293696	None	None	N
N/V	0.1063	likely_benign	0.1083	benign	-0.25	Destabilizing	0.329	N	0.511	neutral	None	None	None	None	N
N/W	0.663	likely_pathogenic	0.686	pathogenic	-0.569	Destabilizing	0.995	D	0.618	neutral	None	None	None	None	N
N/Y	0.1081	likely_benign	0.1111	benign	-0.178	Destabilizing	0.975	D	0.573	neutral	N	0.418439716	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.