TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22247	66964;66965;66966	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
N2AB	20606	62041;62042;62043	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
N2A	19679	59260;59261;59262	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
N2B	13182	39769;39770;39771	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
Novex-1	13307	40144;40145;40146	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
Novex-2	13374	40345;40346;40347	chr2:178581529;178581528;178581527	chr2:179446256;179446255;179446254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-49
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.5615
• 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
P/L	rs749070757	-0.077	0.974	N	0.655	0.367	0.408307896497	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs749070757	-0.077	0.974	N	0.655	0.367	0.408307896497	gnomAD-4.0.0	3.43944E-06	None	None	None	None	I	None	3.00228E-05	0	None	0	0	None	0	0	3.61575E-06	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
P/A	0.1675	likely_benign	0.1564	benign	-0.439	Destabilizing	0.841	D	0.687	prob.delet.	N	0.461130753	None	None	I
P/C	0.772	likely_pathogenic	0.7628	pathogenic	-0.319	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
P/D	0.7063	likely_pathogenic	0.7058	pathogenic	-0.662	Destabilizing	0.98	D	0.732	deleterious	None	None	None	None	I
P/E	0.5032	ambiguous	0.492	ambiguous	-0.779	Destabilizing	0.961	D	0.697	prob.delet.	None	None	None	None	I
P/F	0.7898	likely_pathogenic	0.7848	pathogenic	-0.77	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
P/G	0.5136	ambiguous	0.5154	ambiguous	-0.567	Destabilizing	0.98	D	0.629	neutral	None	None	None	None	I
P/H	0.4857	ambiguous	0.4767	ambiguous	-0.304	Destabilizing	0.997	D	0.745	deleterious	None	None	None	None	I
P/I	0.5533	ambiguous	0.5267	ambiguous	-0.243	Destabilizing	0.99	D	0.74	deleterious	None	None	None	None	I
P/K	0.5338	ambiguous	0.5228	ambiguous	-0.464	Destabilizing	0.092	N	0.361	neutral	None	None	None	None	I
P/L	0.2603	likely_benign	0.2501	benign	-0.243	Destabilizing	0.974	D	0.655	prob.neutral	N	0.467091781	None	None	I
P/M	0.5106	ambiguous	0.4988	ambiguous	-0.274	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
P/N	0.6096	likely_pathogenic	0.5933	pathogenic	-0.043	Destabilizing	0.98	D	0.631	neutral	None	None	None	None	I
P/Q	0.3463	ambiguous	0.3366	benign	-0.317	Destabilizing	0.974	D	0.663	prob.neutral	N	0.478780935	None	None	I
P/R	0.4458	ambiguous	0.4454	ambiguous	0.046	Stabilizing	0.949	D	0.669	prob.neutral	N	0.478020467	None	None	I
P/S	0.2786	likely_benign	0.2701	benign	-0.288	Destabilizing	0.974	D	0.681	prob.neutral	N	0.436742853	None	None	I
P/T	0.2112	likely_benign	0.2016	benign	-0.318	Destabilizing	0.974	D	0.655	prob.neutral	N	0.485939522	None	None	I
P/V	0.3924	ambiguous	0.382	ambiguous	-0.275	Destabilizing	0.98	D	0.653	prob.neutral	None	None	None	None	I
P/W	0.8835	likely_pathogenic	0.8928	pathogenic	-0.888	Destabilizing	0.999	D	0.72	deleterious	None	None	None	None	I
P/Y	0.7721	likely_pathogenic	0.7726	pathogenic	-0.578	Destabilizing	0.999	D	0.75	deleterious	None	None	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.