TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5605	17038;17039;17040	chr2:178732156;178732155;178732154	chr2:179596883;179596882;179596881
N2AB	5288	16087;16088;16089	chr2:178732156;178732155;178732154	chr2:179596883;179596882;179596881
N2A	4361	13306;13307;13308	chr2:178732156;178732155;178732154	chr2:179596883;179596882;179596881
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-39
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.7196
• 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
D/N	None	None	0.001	N	0.275	0.163	0.0884992946249	gnomAD-4.0.0	2.73689E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69848E-06	0	1.65651E-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
D/A	0.0989	likely_benign	0.1137	benign	-0.325	Destabilizing	0.012	N	0.374	neutral	N	0.463155876	None	None	N
D/C	0.4141	ambiguous	0.4492	ambiguous	0.182	Stabilizing	0.864	D	0.367	neutral	None	None	None	None	N
D/E	0.1143	likely_benign	0.1212	benign	-0.282	Destabilizing	None	N	0.167	neutral	N	0.407339878	None	None	N
D/F	0.4036	ambiguous	0.4409	ambiguous	-0.449	Destabilizing	0.628	D	0.387	neutral	None	None	None	None	N
D/G	0.0978	likely_benign	0.1061	benign	-0.495	Destabilizing	0.012	N	0.346	neutral	N	0.424656203	None	None	N
D/H	0.1505	likely_benign	0.1634	benign	-0.384	Destabilizing	0.295	N	0.324	neutral	N	0.468793769	None	None	N
D/I	0.2804	likely_benign	0.3151	benign	0.068	Stabilizing	0.356	N	0.418	neutral	None	None	None	None	N
D/K	0.1965	likely_benign	0.2189	benign	0.367	Stabilizing	0.001	N	0.195	neutral	None	None	None	None	N
D/L	0.2806	likely_benign	0.3105	benign	0.068	Stabilizing	0.072	N	0.466	neutral	None	None	None	None	N
D/M	0.4271	ambiguous	0.464	ambiguous	0.333	Stabilizing	0.628	D	0.369	neutral	None	None	None	None	N
D/N	0.0721	likely_benign	0.0735	benign	0.175	Stabilizing	0.001	N	0.275	neutral	N	0.371627008	None	None	N
D/P	0.5822	likely_pathogenic	0.6385	pathogenic	-0.042	Destabilizing	0.136	N	0.395	neutral	None	None	None	None	N
D/Q	0.2028	likely_benign	0.2229	benign	0.171	Stabilizing	0.003	N	0.27	neutral	None	None	None	None	N
D/R	0.2018	likely_benign	0.227	benign	0.413	Stabilizing	0.038	N	0.431	neutral	None	None	None	None	N
D/S	0.0852	likely_benign	0.0912	benign	0.059	Stabilizing	None	N	0.141	neutral	None	None	None	None	N
D/T	0.1562	likely_benign	0.175	benign	0.187	Stabilizing	0.038	N	0.347	neutral	None	None	None	None	N
D/V	0.1683	likely_benign	0.1907	benign	-0.042	Destabilizing	0.055	N	0.441	neutral	N	0.512237902	None	None	N
D/W	0.7138	likely_pathogenic	0.7543	pathogenic	-0.361	Destabilizing	0.864	D	0.475	neutral	None	None	None	None	N
D/Y	0.1553	likely_benign	0.1669	benign	-0.224	Destabilizing	0.56	D	0.392	neutral	N	0.488630324	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.