TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9706	29341;29342;29343	chr2:178706880;178706879;178706878	chr2:179571607;179571606;179571605
N2AB	9389	28390;28391;28392	chr2:178706880;178706879;178706878	chr2:179571607;179571606;179571605
N2A	8462	25609;25610;25611	chr2:178706880;178706879;178706878	chr2:179571607;179571606;179571605
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-83
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5569
• 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
S/N	None	None	0.023	None	0.139	0.051	0.110078149338	gnomAD-4.0.0	1.59501E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	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
S/A	0.2615	likely_benign	0.1937	benign	-0.373	Destabilizing	0.013	N	0.08	neutral	None	None	None	None	N
S/C	0.5061	ambiguous	0.321	benign	-0.408	Destabilizing	0.993	D	0.347	neutral	None	None	None	None	N
S/D	0.6243	likely_pathogenic	0.4303	ambiguous	0.28	Stabilizing	0.007	N	0.111	neutral	None	None	None	None	N
S/E	0.8874	likely_pathogenic	0.7598	pathogenic	0.231	Stabilizing	0.329	N	0.212	neutral	None	None	None	None	N
S/F	0.8955	likely_pathogenic	0.7185	pathogenic	-0.87	Destabilizing	0.981	D	0.391	neutral	None	None	None	None	N
S/G	0.2456	likely_benign	0.138	benign	-0.531	Destabilizing	0.425	N	0.271	neutral	None	None	None	None	N
S/H	0.8249	likely_pathogenic	0.6291	pathogenic	-0.893	Destabilizing	0.944	D	0.35	neutral	None	None	None	None	N
S/I	0.7762	likely_pathogenic	0.5054	ambiguous	-0.083	Destabilizing	0.863	D	0.432	neutral	None	None	None	None	N
S/K	0.9735	likely_pathogenic	0.8946	pathogenic	-0.402	Destabilizing	0.704	D	0.197	neutral	None	None	None	None	N
S/L	0.6406	likely_pathogenic	0.3853	ambiguous	-0.083	Destabilizing	0.704	D	0.355	neutral	None	None	None	None	N
S/M	0.7193	likely_pathogenic	0.5005	ambiguous	-0.143	Destabilizing	0.981	D	0.347	neutral	None	None	None	None	N
S/N	0.2228	likely_benign	0.1326	benign	-0.283	Destabilizing	0.023	N	0.139	neutral	None	None	None	None	N
S/P	0.383	ambiguous	0.277	benign	-0.148	Destabilizing	0.007	N	0.143	neutral	None	None	None	None	N
S/Q	0.9106	likely_pathogenic	0.7874	pathogenic	-0.407	Destabilizing	0.944	D	0.325	neutral	None	None	None	None	N
S/R	0.9658	likely_pathogenic	0.8644	pathogenic	-0.244	Destabilizing	0.927	D	0.404	neutral	None	None	None	None	N
S/T	0.2785	likely_benign	0.1778	benign	-0.33	Destabilizing	0.023	N	0.115	neutral	None	None	None	None	N
S/V	0.7674	likely_pathogenic	0.5418	ambiguous	-0.148	Destabilizing	0.704	D	0.36	neutral	None	None	None	None	N
S/W	0.916	likely_pathogenic	0.7911	pathogenic	-0.921	Destabilizing	0.995	D	0.467	neutral	None	None	None	None	N
S/Y	0.7917	likely_pathogenic	0.5755	pathogenic	-0.602	Destabilizing	0.981	D	0.391	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.