TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18234	54925;54926;54927	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
N2AB	16593	50002;50003;50004	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
N2A	15666	47221;47222;47223	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
N2B	9169	27730;27731;27732	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
Novex-1	9294	28105;28106;28107	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
Novex-2	9361	28306;28307;28308	chr2:178603987;178603986;178603985	chr2:179468714;179468713;179468712
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: Fn3-20
• Domain position: 69
• Structural Position: 94
• Q(SASA): 0.4418
• 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/T	rs1060500416	None	0.891	N	0.485	0.182	0.305410167561	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs1060500416	None	0.891	N	0.485	0.182	0.305410167561	gnomAD-4.0.0	6.58371E-06	None	None	None	None	N	None	2.41639E-05	0	None	0	0	None	0	0	0	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
P/A	0.1797	likely_benign	0.1052	benign	-1.063	Destabilizing	0.625	D	0.427	neutral	N	0.45881721	None	None	N
P/C	0.7545	likely_pathogenic	0.6038	pathogenic	-0.904	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	N
P/D	0.818	likely_pathogenic	0.6531	pathogenic	-0.445	Destabilizing	0.991	D	0.588	neutral	None	None	None	None	N
P/E	0.6134	likely_pathogenic	0.42	ambiguous	-0.473	Destabilizing	0.971	D	0.546	neutral	None	None	None	None	N
P/F	0.7864	likely_pathogenic	0.5251	ambiguous	-0.842	Destabilizing	0.949	D	0.592	neutral	None	None	None	None	N
P/G	0.469	ambiguous	0.2945	benign	-1.33	Destabilizing	0.971	D	0.526	neutral	None	None	None	None	N
P/H	0.5179	ambiguous	0.2856	benign	-0.74	Destabilizing	0.997	D	0.567	neutral	N	0.471285075	None	None	N
P/I	0.5495	ambiguous	0.3103	benign	-0.458	Destabilizing	0.525	D	0.48	neutral	None	None	None	None	N
P/K	0.7021	likely_pathogenic	0.4954	ambiguous	-0.84	Destabilizing	0.915	D	0.496	neutral	None	None	None	None	N
P/L	0.2268	likely_benign	0.1044	benign	-0.458	Destabilizing	0.002	N	0.495	neutral	N	0.426379504	None	None	N
P/M	0.5053	ambiguous	0.2986	benign	-0.492	Destabilizing	0.949	D	0.593	neutral	None	None	None	None	N
P/N	0.5754	likely_pathogenic	0.3836	ambiguous	-0.641	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
P/Q	0.3514	ambiguous	0.1934	benign	-0.791	Destabilizing	0.991	D	0.584	neutral	None	None	None	None	N
P/R	0.5974	likely_pathogenic	0.3555	ambiguous	-0.349	Destabilizing	0.966	D	0.595	neutral	N	0.441962245	None	None	N
P/S	0.2632	likely_benign	0.1457	benign	-1.187	Destabilizing	0.891	D	0.471	neutral	N	0.424317847	None	None	N
P/T	0.1984	likely_benign	0.114	benign	-1.093	Destabilizing	0.891	D	0.485	neutral	N	0.373176951	None	None	N
P/V	0.3795	ambiguous	0.2059	benign	-0.623	Destabilizing	0.525	D	0.439	neutral	None	None	None	None	N
P/W	0.8855	likely_pathogenic	0.685	pathogenic	-0.951	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
P/Y	0.7648	likely_pathogenic	0.5146	ambiguous	-0.662	Destabilizing	0.974	D	0.589	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.