TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24404	73435;73436;73437	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
N2AB	22763	68512;68513;68514	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
N2A	21836	65731;65732;65733	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
N2B	15339	46240;46241;46242	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
Novex-1	15464	46615;46616;46617	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
Novex-2	15531	46816;46817;46818	chr2:178572922;178572921;178572920	chr2:179437649;179437648;179437647
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-65
• Domain position: 82
• Structural Position: 113
• Q(SASA): 0.6527
• Predicted PPI site: I

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/Y	None	None	0.873	N	0.527	0.372	0.603539076606	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99593E-07	1.15939E-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
S/A	0.0627	likely_benign	0.0626	benign	-0.322	Destabilizing	0.001	N	0.063	neutral	N	0.444405118	None	None	I
S/C	0.0814	likely_benign	0.0803	benign	-0.236	Destabilizing	0.003	N	0.178	neutral	N	0.468432723	None	None	I
S/D	0.2797	likely_benign	0.3302	benign	-0.028	Destabilizing	0.561	D	0.329	neutral	None	None	None	None	I
S/E	0.328	likely_benign	0.3665	ambiguous	-0.145	Destabilizing	0.39	N	0.279	neutral	None	None	None	None	I
S/F	0.1969	likely_benign	0.2204	benign	-1.06	Destabilizing	0.772	D	0.525	neutral	N	0.494930769	None	None	I
S/G	0.0698	likely_benign	0.073	benign	-0.368	Destabilizing	0.209	N	0.293	neutral	None	None	None	None	I
S/H	0.2315	likely_benign	0.2753	benign	-0.826	Destabilizing	0.965	D	0.412	neutral	None	None	None	None	I
S/I	0.1107	likely_benign	0.1132	benign	-0.332	Destabilizing	0.004	N	0.422	neutral	None	None	None	None	I
S/K	0.3027	likely_benign	0.3625	ambiguous	-0.336	Destabilizing	0.004	N	0.156	neutral	None	None	None	None	I
S/L	0.0828	likely_benign	0.0841	benign	-0.332	Destabilizing	0.083	N	0.53	neutral	None	None	None	None	I
S/M	0.1387	likely_benign	0.1362	benign	-0.019	Destabilizing	0.818	D	0.425	neutral	None	None	None	None	I
S/N	0.0966	likely_benign	0.1057	benign	-0.068	Destabilizing	0.561	D	0.347	neutral	None	None	None	None	I
S/P	0.2897	likely_benign	0.3494	ambiguous	-0.305	Destabilizing	0.873	D	0.434	neutral	N	0.503320135	None	None	I
S/Q	0.2874	likely_benign	0.3338	benign	-0.375	Destabilizing	0.818	D	0.321	neutral	None	None	None	None	I
S/R	0.255	likely_benign	0.3227	benign	-0.085	Destabilizing	0.39	N	0.456	neutral	None	None	None	None	I
S/T	0.0693	likely_benign	0.071	benign	-0.197	Destabilizing	0.285	N	0.305	neutral	N	0.512091547	None	None	I
S/V	0.118	likely_benign	0.1219	benign	-0.305	Destabilizing	0.083	N	0.519	neutral	None	None	None	None	I
S/W	0.3531	ambiguous	0.3932	ambiguous	-1.078	Destabilizing	0.991	D	0.548	neutral	None	None	None	None	I
S/Y	0.18	likely_benign	0.2063	benign	-0.787	Destabilizing	0.873	D	0.527	neutral	N	0.48818282	None	None	I

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.