TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32486	97681;97682;97683	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
N2AB	30845	92758;92759;92760	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
N2A	29918	89977;89978;89979	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
N2B	23421	70486;70487;70488	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
Novex-1	23546	70861;70862;70863	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
Novex-2	23613	71062;71063;71064	chr2:178542300;178542299;178542298	chr2:179407027;179407026;179407025
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: Fn3-124
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.4364
• 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
L/V	rs769778547	-0.767	0.997	N	0.714	0.169	0.442160178816	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.33E-05	None	0	0	0
L/V	rs769778547	-0.767	0.997	N	0.714	0.169	0.442160178816	gnomAD-4.0.0	1.59606E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44155E-05	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	0.5954	likely_pathogenic	0.494	ambiguous	-2.215	Highly Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	I
L/C	0.6298	likely_pathogenic	0.5474	ambiguous	-1.396	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
L/D	0.9827	likely_pathogenic	0.9704	pathogenic	-1.986	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	I
L/E	0.8159	likely_pathogenic	0.7413	pathogenic	-1.827	Destabilizing	0.999	D	0.921	deleterious	None	None	None	None	I
L/F	0.6107	likely_pathogenic	0.5163	ambiguous	-1.273	Destabilizing	0.999	D	0.781	deleterious	N	0.506897683	None	None	I
L/G	0.9002	likely_pathogenic	0.843	pathogenic	-2.702	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	I
L/H	0.7212	likely_pathogenic	0.6164	pathogenic	-2.045	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I
L/I	0.1232	likely_benign	0.112	benign	-0.852	Destabilizing	0.998	D	0.674	prob.neutral	None	None	None	None	I
L/K	0.7062	likely_pathogenic	0.6308	pathogenic	-1.595	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	I
L/M	0.2343	likely_benign	0.1992	benign	-0.745	Destabilizing	0.999	D	0.768	deleterious	N	0.491791942	None	None	I
L/N	0.879	likely_pathogenic	0.827	pathogenic	-1.692	Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	I
L/P	0.9892	likely_pathogenic	0.985	pathogenic	-1.282	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	I
L/Q	0.4441	ambiguous	0.3385	benign	-1.653	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	I
L/R	0.5705	likely_pathogenic	0.45	ambiguous	-1.236	Destabilizing	0.999	D	0.934	deleterious	None	None	None	None	I
L/S	0.7312	likely_pathogenic	0.6015	pathogenic	-2.419	Highly Destabilizing	0.999	D	0.887	deleterious	N	0.478278123	None	None	I
L/T	0.4331	ambiguous	0.363	ambiguous	-2.126	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
L/V	0.1422	likely_benign	0.1225	benign	-1.282	Destabilizing	0.997	D	0.714	prob.delet.	N	0.511217261	None	None	I
L/W	0.8463	likely_pathogenic	0.771	pathogenic	-1.563	Destabilizing	1.0	D	0.875	deleterious	D	0.530370763	None	None	I
L/Y	0.8483	likely_pathogenic	0.7741	pathogenic	-1.281	Destabilizing	0.999	D	0.891	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.