TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30172	90739;90740;90741	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
N2AB	28531	85816;85817;85818	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
N2A	27604	83035;83036;83037	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
N2B	21107	63544;63545;63546	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
Novex-1	21232	63919;63920;63921	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
Novex-2	21299	64120;64121;64122	chr2:178552386;178552385;178552384	chr2:179417113;179417112;179417111
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-148
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2498
• 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/M	rs1392178250	-0.785	0.983	N	0.612	0.527	0.593458155424	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/P	None	None	0.994	D	0.792	0.765	0.894442926721	gnomAD-4.0.0	1.39005E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.82008E-06	0	0
L/R	None	None	0.983	D	0.767	0.82	0.87732752342	gnomAD-4.0.0	6.95025E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.68651E-05

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	0.8272	likely_pathogenic	0.8004	pathogenic	-2.447	Highly Destabilizing	0.845	D	0.476	neutral	None	None	None	None	N
L/C	0.851	likely_pathogenic	0.8398	pathogenic	-1.58	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
L/D	0.9963	likely_pathogenic	0.9949	pathogenic	-2.815	Highly Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
L/E	0.9638	likely_pathogenic	0.955	pathogenic	-2.593	Highly Destabilizing	0.987	D	0.782	deleterious	None	None	None	None	N
L/F	0.5685	likely_pathogenic	0.4939	ambiguous	-1.548	Destabilizing	0.073	N	0.349	neutral	None	None	None	None	N
L/G	0.974	likely_pathogenic	0.967	pathogenic	-2.95	Highly Destabilizing	0.987	D	0.766	deleterious	None	None	None	None	N
L/H	0.9514	likely_pathogenic	0.937	pathogenic	-2.293	Highly Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
L/I	0.1544	likely_benign	0.1468	benign	-0.994	Destabilizing	0.653	D	0.447	neutral	None	None	None	None	N
L/K	0.9526	likely_pathogenic	0.9442	pathogenic	-1.972	Destabilizing	0.987	D	0.739	prob.delet.	None	None	None	None	N
L/M	0.2648	likely_benign	0.246	benign	-0.819	Destabilizing	0.983	D	0.612	neutral	N	0.516494286	None	None	N
L/N	0.9783	likely_pathogenic	0.9719	pathogenic	-2.301	Highly Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
L/P	0.9596	likely_pathogenic	0.9513	pathogenic	-1.461	Destabilizing	0.994	D	0.792	deleterious	D	0.525243699	None	None	N
L/Q	0.8684	likely_pathogenic	0.8439	pathogenic	-2.188	Highly Destabilizing	0.994	D	0.759	deleterious	D	0.529282624	None	None	N
L/R	0.9288	likely_pathogenic	0.9206	pathogenic	-1.686	Destabilizing	0.983	D	0.767	deleterious	D	0.540385439	None	None	N
L/S	0.9543	likely_pathogenic	0.9404	pathogenic	-2.927	Highly Destabilizing	0.975	D	0.729	prob.delet.	None	None	None	None	N
L/T	0.8641	likely_pathogenic	0.843	pathogenic	-2.56	Highly Destabilizing	0.975	D	0.63	neutral	None	None	None	None	N
L/V	0.1596	likely_benign	0.1557	benign	-1.461	Destabilizing	0.025	N	0.355	neutral	D	0.527560511	None	None	N
L/W	0.8991	likely_pathogenic	0.8772	pathogenic	-1.881	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/Y	0.9156	likely_pathogenic	0.8918	pathogenic	-1.578	Destabilizing	0.95	D	0.678	prob.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.