TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4813	14662;14663;14664	chr2:178736009;178736008;178736007	chr2:179600736;179600735;179600734
N2AB	4496	13711;13712;13713	chr2:178736009;178736008;178736007	chr2:179600736;179600735;179600734
N2A	3569	10930;10931;10932	chr2:178736009;178736008;178736007	chr2:179600736;179600735;179600734
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-31
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5902
• 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
K/Q	None	None	0.136	N	0.365	0.139	0.12205267543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	None	None	0.012	N	0.336	0.075	0.173771789658	gnomAD-4.0.0	1.5934E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88352E-05	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
K/A	0.4168	ambiguous	0.4386	ambiguous	-0.526	Destabilizing	0.688	D	0.495	neutral	None	None	None	None	N
K/C	0.7412	likely_pathogenic	0.7574	pathogenic	-0.648	Destabilizing	0.998	D	0.512	neutral	None	None	None	None	N
K/D	0.7169	likely_pathogenic	0.7597	pathogenic	0.007	Stabilizing	0.842	D	0.545	neutral	None	None	None	None	N
K/E	0.2185	likely_benign	0.2561	benign	0.129	Stabilizing	0.454	N	0.56	neutral	N	0.446048418	None	None	N
K/F	0.8605	likely_pathogenic	0.8729	pathogenic	-0.216	Destabilizing	0.949	D	0.54	neutral	None	None	None	None	N
K/G	0.6029	likely_pathogenic	0.6351	pathogenic	-0.875	Destabilizing	0.915	D	0.527	neutral	None	None	None	None	N
K/H	0.3441	ambiguous	0.3429	ambiguous	-0.994	Destabilizing	0.974	D	0.548	neutral	None	None	None	None	N
K/I	0.4028	ambiguous	0.4344	ambiguous	0.373	Stabilizing	0.728	D	0.521	neutral	None	None	None	None	N
K/L	0.4666	ambiguous	0.5015	ambiguous	0.373	Stabilizing	0.016	N	0.405	neutral	None	None	None	None	N
K/M	0.2936	likely_benign	0.328	benign	0.02	Stabilizing	0.934	D	0.559	neutral	N	0.445622501	None	None	N
K/N	0.4556	ambiguous	0.5198	ambiguous	-0.479	Destabilizing	0.801	D	0.545	neutral	N	0.443471533	None	None	N
K/P	0.9187	likely_pathogenic	0.9309	pathogenic	0.103	Stabilizing	0.991	D	0.581	neutral	None	None	None	None	N
K/Q	0.1526	likely_benign	0.1582	benign	-0.468	Destabilizing	0.136	N	0.365	neutral	N	0.443863423	None	None	N
K/R	0.0845	likely_benign	0.0815	benign	-0.429	Destabilizing	0.012	N	0.336	neutral	N	0.415302168	None	None	N
K/S	0.4195	ambiguous	0.452	ambiguous	-1.104	Destabilizing	0.842	D	0.535	neutral	None	None	None	None	N
K/T	0.1559	likely_benign	0.1667	benign	-0.772	Destabilizing	0.801	D	0.534	neutral	N	0.343323217	None	None	N
K/V	0.3542	ambiguous	0.3638	ambiguous	0.103	Stabilizing	0.029	N	0.426	neutral	None	None	None	None	N
K/W	0.8448	likely_pathogenic	0.8605	pathogenic	-0.134	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
K/Y	0.7043	likely_pathogenic	0.7418	pathogenic	0.154	Stabilizing	0.991	D	0.541	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.