TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17317	52174;52175;52176	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
N2AB	15676	47251;47252;47253	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
N2A	14749	44470;44471;44472	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
N2B	8252	24979;24980;24981	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
Novex-1	8377	25354;25355;25356	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
Novex-2	8444	25555;25556;25557	chr2:178609361;178609360;178609359	chr2:179474088;179474087;179474086
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-112
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.2709
• 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
P/S	None	None	0.007	N	0.159	0.035	0.119812018005	gnomAD-4.0.0	1.59462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86393E-06	0	0
P/T	None	None	0.007	N	0.145	0.032	0.136095386433	gnomAD-4.0.0	1.59462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03177E-05

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
P/A	0.1271	likely_benign	0.1451	benign	-0.891	Destabilizing	0.201	N	0.353	neutral	N	0.513387987	None	None	N
P/C	0.5155	ambiguous	0.5783	pathogenic	-0.771	Destabilizing	0.992	D	0.453	neutral	None	None	None	None	N
P/D	0.3866	ambiguous	0.4149	ambiguous	-0.506	Destabilizing	0.617	D	0.373	neutral	None	None	None	None	N
P/E	0.2985	likely_benign	0.3353	benign	-0.557	Destabilizing	0.617	D	0.314	neutral	None	None	None	None	N
P/F	0.6468	likely_pathogenic	0.7002	pathogenic	-0.733	Destabilizing	0.85	D	0.485	neutral	None	None	None	None	N
P/G	0.2751	likely_benign	0.313	benign	-1.125	Destabilizing	0.447	N	0.396	neutral	None	None	None	None	N
P/H	0.2413	likely_benign	0.2663	benign	-0.514	Destabilizing	0.97	D	0.429	neutral	N	0.482291606	None	None	N
P/I	0.5498	ambiguous	0.6072	pathogenic	-0.39	Destabilizing	0.447	N	0.453	neutral	None	None	None	None	N
P/K	0.3528	ambiguous	0.4062	ambiguous	-0.804	Destabilizing	0.447	N	0.313	neutral	None	None	None	None	N
P/L	0.2089	likely_benign	0.2381	benign	-0.39	Destabilizing	0.004	N	0.319	neutral	N	0.489128461	None	None	N
P/M	0.4861	ambiguous	0.5339	ambiguous	-0.415	Destabilizing	0.85	D	0.441	neutral	None	None	None	None	N
P/N	0.3053	likely_benign	0.3451	ambiguous	-0.601	Destabilizing	0.447	N	0.42	neutral	None	None	None	None	N
P/Q	0.2061	likely_benign	0.2445	benign	-0.786	Destabilizing	0.85	D	0.411	neutral	None	None	None	None	N
P/R	0.2724	likely_benign	0.3058	benign	-0.249	Destabilizing	0.81	D	0.439	neutral	N	0.508174168	None	None	N
P/S	0.1246	likely_benign	0.1293	benign	-1.073	Destabilizing	0.007	N	0.159	neutral	N	0.491223204	None	None	N
P/T	0.1339	likely_benign	0.1505	benign	-1.014	Destabilizing	0.007	N	0.145	neutral	N	0.477293901	None	None	N
P/V	0.3581	ambiguous	0.4089	ambiguous	-0.52	Destabilizing	0.447	N	0.399	neutral	None	None	None	None	N
P/W	0.7377	likely_pathogenic	0.7809	pathogenic	-0.845	Destabilizing	0.992	D	0.514	neutral	None	None	None	None	N
P/Y	0.5189	ambiguous	0.5641	pathogenic	-0.564	Destabilizing	0.972	D	0.495	neutral	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.