TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14469	43630;43631;43632	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
N2AB	12828	38707;38708;38709	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
N2A	11901	35926;35927;35928	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
N2B	5404	16435;16436;16437	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
Novex-1	5529	16810;16811;16812	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
Novex-2	5596	17011;17012;17013	chr2:178632601;178632600;178632599	chr2:179497328;179497327;179497326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-95
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.1693
• 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
A/G	None	None	0.911	D	0.574	0.549	0.405422107966	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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
A/C	0.618	likely_pathogenic	0.5635	ambiguous	-1.536	Destabilizing	0.994	D	0.748	deleterious	None	None	None	None	N
A/D	0.9569	likely_pathogenic	0.9565	pathogenic	-2.215	Highly Destabilizing	0.973	D	0.766	deleterious	D	0.645343099	None	None	N
A/E	0.9206	likely_pathogenic	0.9229	pathogenic	-2.178	Highly Destabilizing	0.979	D	0.745	deleterious	None	None	None	None	N
A/F	0.8479	likely_pathogenic	0.8467	pathogenic	-1.157	Destabilizing	0.959	D	0.778	deleterious	None	None	None	None	N
A/G	0.4154	ambiguous	0.3952	ambiguous	-1.481	Destabilizing	0.911	D	0.574	neutral	D	0.6452355	None	None	N
A/H	0.9665	likely_pathogenic	0.9645	pathogenic	-1.551	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
A/I	0.3218	likely_benign	0.3281	benign	-0.413	Destabilizing	0.535	D	0.631	neutral	None	None	None	None	N
A/K	0.9656	likely_pathogenic	0.9666	pathogenic	-1.353	Destabilizing	0.979	D	0.744	deleterious	None	None	None	None	N
A/L	0.3304	likely_benign	0.3069	benign	-0.413	Destabilizing	0.769	D	0.521	neutral	None	None	None	None	N
A/M	0.4839	ambiguous	0.4648	ambiguous	-0.519	Destabilizing	0.989	D	0.766	deleterious	None	None	None	None	N
A/N	0.8691	likely_pathogenic	0.8657	pathogenic	-1.368	Destabilizing	0.993	D	0.778	deleterious	None	None	None	None	N
A/P	0.6874	likely_pathogenic	0.6089	pathogenic	-0.625	Destabilizing	0.991	D	0.77	deleterious	D	0.549676027	None	None	N
A/Q	0.9223	likely_pathogenic	0.9183	pathogenic	-1.489	Destabilizing	0.993	D	0.774	deleterious	None	None	None	None	N
A/R	0.9327	likely_pathogenic	0.931	pathogenic	-1.074	Destabilizing	0.979	D	0.771	deleterious	None	None	None	None	N
A/S	0.2181	likely_benign	0.2171	benign	-1.739	Destabilizing	0.834	D	0.586	neutral	N	0.513060941	None	None	N
A/T	0.1137	likely_benign	0.1149	benign	-1.605	Destabilizing	0.716	D	0.609	neutral	D	0.522805507	None	None	N
A/V	0.0974	likely_benign	0.0997	benign	-0.625	Destabilizing	0.016	N	0.305	neutral	N	0.438632189	None	None	N
A/W	0.9872	likely_pathogenic	0.985	pathogenic	-1.577	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
A/Y	0.9581	likely_pathogenic	0.9552	pathogenic	-1.151	Destabilizing	0.979	D	0.783	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.