TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6789	20590;20591;20592	chr2:178725957;178725956;178725955	chr2:179590684;179590683;179590682
N2AB	6472	19639;19640;19641	chr2:178725957;178725956;178725955	chr2:179590684;179590683;179590682
N2A	5545	16858;16859;16860	chr2:178725957;178725956;178725955	chr2:179590684;179590683;179590682
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: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-52
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7327
• 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
P/L	rs1480351925	0.098	1.0	N	0.689	0.466	0.813777372686	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
P/L	rs1480351925	0.098	1.0	N	0.689	0.466	0.813777372686	gnomAD-4.0.0	1.02734E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35015E-05	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	0.2706	likely_benign	0.3563	ambiguous	-0.641	Destabilizing	0.996	D	0.658	neutral	N	0.517415301	None	None	N
P/C	0.9156	likely_pathogenic	0.9551	pathogenic	-0.485	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
P/D	0.7995	likely_pathogenic	0.8507	pathogenic	-0.686	Destabilizing	0.996	D	0.669	neutral	None	None	None	None	N
P/E	0.6834	likely_pathogenic	0.7759	pathogenic	-0.775	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
P/F	0.8963	likely_pathogenic	0.9397	pathogenic	-0.769	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
P/G	0.7343	likely_pathogenic	0.7887	pathogenic	-0.807	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
P/H	0.627	likely_pathogenic	0.7327	pathogenic	-0.424	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
P/I	0.7415	likely_pathogenic	0.799	pathogenic	-0.332	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
P/K	0.77	likely_pathogenic	0.8427	pathogenic	-0.638	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
P/L	0.4215	ambiguous	0.5534	ambiguous	-0.332	Destabilizing	1.0	D	0.689	prob.neutral	N	0.502987344	None	None	N
P/M	0.7556	likely_pathogenic	0.8227	pathogenic	-0.409	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
P/N	0.7328	likely_pathogenic	0.7881	pathogenic	-0.283	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
P/Q	0.548	ambiguous	0.6574	pathogenic	-0.522	Destabilizing	1.0	D	0.652	neutral	N	0.485804461	None	None	N
P/R	0.5911	likely_pathogenic	0.7065	pathogenic	-0.119	Destabilizing	1.0	D	0.675	prob.neutral	N	0.49525189	None	None	N
P/S	0.4413	ambiguous	0.5493	ambiguous	-0.586	Destabilizing	1.0	D	0.693	prob.neutral	N	0.48807264	None	None	N
P/T	0.3981	ambiguous	0.4782	ambiguous	-0.582	Destabilizing	0.999	D	0.685	prob.neutral	D	0.531709963	None	None	N
P/V	0.5881	likely_pathogenic	0.657	pathogenic	-0.401	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
P/W	0.9619	likely_pathogenic	0.9791	pathogenic	-0.885	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
P/Y	0.8726	likely_pathogenic	0.9176	pathogenic	-0.594	Destabilizing	1.0	D	0.638	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.