TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15370	46333;46334;46335	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
N2AB	13729	41410;41411;41412	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
N2A	12802	38629;38630;38631	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
N2B	6305	19138;19139;19140	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
Novex-1	6430	19513;19514;19515	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
Novex-2	6497	19714;19715;19716	chr2:178620413;178620412;178620411	chr2:179485140;179485139;179485138
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-105
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.1907
• 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
E/V	None	None	1.0	N	0.797	0.486	0.581503058331	gnomAD-4.0.0	1.59445E-06	None	None	None	None	N	None	0	0	None	0	2.77994E-05	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
E/A	0.3931	ambiguous	0.3622	ambiguous	-1.052	Destabilizing	0.999	D	0.703	prob.neutral	D	0.596385455	None	None	N
E/C	0.9339	likely_pathogenic	0.933	pathogenic	-0.501	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/D	0.3426	ambiguous	0.3441	ambiguous	-1.149	Destabilizing	0.999	D	0.536	neutral	D	0.572352185	None	None	N
E/F	0.8919	likely_pathogenic	0.8811	pathogenic	-0.598	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/G	0.4927	ambiguous	0.4568	ambiguous	-1.41	Destabilizing	1.0	D	0.753	deleterious	D	0.638978297	None	None	N
E/H	0.7747	likely_pathogenic	0.7207	pathogenic	-0.859	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/I	0.5395	ambiguous	0.5207	ambiguous	-0.07	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/K	0.317	likely_benign	0.2617	benign	-0.6	Destabilizing	0.999	D	0.617	neutral	N	0.505254958	None	None	N
E/L	0.6778	likely_pathogenic	0.6455	pathogenic	-0.07	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/M	0.6698	likely_pathogenic	0.6367	pathogenic	0.464	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/N	0.5162	ambiguous	0.4775	ambiguous	-1.068	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.8787	likely_pathogenic	0.8721	pathogenic	-0.377	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Q	0.263	likely_benign	0.2173	benign	-0.957	Destabilizing	1.0	D	0.616	neutral	N	0.511065735	None	None	N
E/R	0.4791	ambiguous	0.413	ambiguous	-0.376	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/S	0.445	ambiguous	0.4145	ambiguous	-1.411	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
E/T	0.417	ambiguous	0.3817	ambiguous	-1.104	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/V	0.3918	ambiguous	0.3695	ambiguous	-0.377	Destabilizing	1.0	D	0.797	deleterious	N	0.501260443	None	None	N
E/W	0.9673	likely_pathogenic	0.963	pathogenic	-0.33	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/Y	0.8495	likely_pathogenic	0.8225	pathogenic	-0.326	Destabilizing	1.0	D	0.813	deleterious	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.