TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5019	15280;15281;15282	chr2:178734869;178734868;178734867	chr2:179599596;179599595;179599594
N2AB	4702	14329;14330;14331	chr2:178734869;178734868;178734867	chr2:179599596;179599595;179599594
N2A	3775	11548;11549;11550	chr2:178734869;178734868;178734867	chr2:179599596;179599595;179599594
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-33
• Domain position: 39
• Structural Position: 52
• Q(SASA): 0.9098
• 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/S	None	None	0.826	N	0.297	0.188	0.104622674875	gnomAD-4.0.0	4.78995E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79899E-06	5.7971E-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	0.3778	ambiguous	0.2906	benign	-0.231	Destabilizing	0.939	D	0.326	neutral	None	None	None	None	N
N/C	0.5102	ambiguous	0.4279	ambiguous	0.192	Stabilizing	0.999	D	0.463	neutral	None	None	None	None	N
N/D	0.1228	likely_benign	0.1058	benign	0.313	Stabilizing	0.015	N	0.143	neutral	N	0.395073778	None	None	N
N/E	0.3883	ambiguous	0.3241	benign	0.264	Stabilizing	0.079	N	0.135	neutral	None	None	None	None	N
N/F	0.7435	likely_pathogenic	0.6548	pathogenic	-0.769	Destabilizing	0.997	D	0.428	neutral	None	None	None	None	N
N/G	0.2185	likely_benign	0.1693	benign	-0.352	Destabilizing	0.863	D	0.267	neutral	None	None	None	None	N
N/H	0.1418	likely_benign	0.1126	benign	-0.329	Destabilizing	0.996	D	0.355	neutral	N	0.443264363	None	None	N
N/I	0.5766	likely_pathogenic	0.4982	ambiguous	-0.011	Destabilizing	0.996	D	0.434	neutral	D	0.569130619	None	None	N
N/K	0.3645	ambiguous	0.2769	benign	0.19	Stabilizing	0.92	D	0.27	neutral	N	0.450266596	None	None	N
N/L	0.4684	ambiguous	0.3836	ambiguous	-0.011	Destabilizing	0.991	D	0.433	neutral	None	None	None	None	N
N/M	0.5384	ambiguous	0.4666	ambiguous	0.114	Stabilizing	0.999	D	0.402	neutral	None	None	None	None	N
N/P	0.9033	likely_pathogenic	0.8549	pathogenic	-0.06	Destabilizing	0.997	D	0.414	neutral	None	None	None	None	N
N/Q	0.3367	likely_benign	0.2652	benign	-0.233	Destabilizing	0.939	D	0.329	neutral	None	None	None	None	N
N/R	0.421	ambiguous	0.319	benign	0.252	Stabilizing	0.939	D	0.345	neutral	None	None	None	None	N
N/S	0.0936	likely_benign	0.0828	benign	-0.054	Destabilizing	0.826	D	0.297	neutral	N	0.450586767	None	None	N
N/T	0.2517	likely_benign	0.2095	benign	0.032	Stabilizing	0.959	D	0.288	neutral	N	0.451358175	None	None	N
N/V	0.5807	likely_pathogenic	0.4815	ambiguous	-0.06	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	N
N/W	0.8685	likely_pathogenic	0.8112	pathogenic	-0.838	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
N/Y	0.2984	likely_benign	0.2422	benign	-0.528	Destabilizing	0.996	D	0.398	neutral	N	0.504133809	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.