TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24958	75097;75098;75099	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
N2AB	23317	70174;70175;70176	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
N2A	22390	67393;67394;67395	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
N2B	15893	47902;47903;47904	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
Novex-1	16018	48277;48278;48279	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
Novex-2	16085	48478;48479;48480	chr2:178571260;178571259;178571258	chr2:179435987;179435986;179435985
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-69
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1918
• 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
L/S	None	None	0.684	N	0.525	0.235	0.602613489494	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	2.28676E-05	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
L/A	0.2723	likely_benign	0.2922	benign	-1.84	Destabilizing	0.373	N	0.457	neutral	None	None	None	None	N
L/C	0.4187	ambiguous	0.4351	ambiguous	-1.145	Destabilizing	0.996	D	0.517	neutral	None	None	None	None	N
L/D	0.8587	likely_pathogenic	0.8728	pathogenic	-1.229	Destabilizing	0.91	D	0.594	neutral	None	None	None	None	N
L/E	0.5148	ambiguous	0.5516	ambiguous	-1.099	Destabilizing	0.59	D	0.545	neutral	None	None	None	None	N
L/F	0.3093	likely_benign	0.3246	benign	-1.017	Destabilizing	0.884	D	0.501	neutral	N	0.512168905	None	None	N
L/G	0.6604	likely_pathogenic	0.6837	pathogenic	-2.282	Highly Destabilizing	0.91	D	0.59	neutral	None	None	None	None	N
L/H	0.4899	ambiguous	0.4956	ambiguous	-1.408	Destabilizing	0.987	D	0.617	neutral	None	None	None	None	N
L/I	0.0806	likely_benign	0.0858	benign	-0.634	Destabilizing	0.037	N	0.309	neutral	None	None	None	None	N
L/K	0.659	likely_pathogenic	0.671	pathogenic	-1.276	Destabilizing	0.59	D	0.523	neutral	None	None	None	None	N
L/M	0.1046	likely_benign	0.1091	benign	-0.574	Destabilizing	0.939	D	0.524	neutral	N	0.521521894	None	None	N
L/N	0.5408	ambiguous	0.5739	pathogenic	-1.373	Destabilizing	0.91	D	0.609	neutral	None	None	None	None	N
L/P	0.8649	likely_pathogenic	0.8712	pathogenic	-1.009	Destabilizing	0.953	D	0.613	neutral	None	None	None	None	N
L/Q	0.2551	likely_benign	0.2785	benign	-1.344	Destabilizing	0.016	N	0.324	neutral	None	None	None	None	N
L/R	0.5776	likely_pathogenic	0.5904	pathogenic	-0.889	Destabilizing	0.835	D	0.583	neutral	None	None	None	None	N
L/S	0.4258	ambiguous	0.4741	ambiguous	-2.1	Highly Destabilizing	0.684	D	0.525	neutral	N	0.46693824	None	None	N
L/T	0.2915	likely_benign	0.3198	benign	-1.826	Destabilizing	0.742	D	0.437	neutral	None	None	None	None	N
L/V	0.085	likely_benign	0.0891	benign	-1.009	Destabilizing	0.007	N	0.23	neutral	N	0.437095143	None	None	N
L/W	0.492	ambiguous	0.4998	ambiguous	-1.2	Destabilizing	0.994	D	0.621	neutral	N	0.511099695	None	None	N
L/Y	0.5345	ambiguous	0.5368	ambiguous	-0.922	Destabilizing	0.953	D	0.521	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.