TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8543	25852;25853;25854	chr2:178717107;178717106;178717105	chr2:179581834;179581833;179581832
N2AB	8226	24901;24902;24903	chr2:178717107;178717106;178717105	chr2:179581834;179581833;179581832
N2A	7299	22120;22121;22122	chr2:178717107;178717106;178717105	chr2:179581834;179581833;179581832
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-70
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1118
• 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/P	None	None	1.0	D	0.863	0.765	0.887417416464	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.8552	likely_pathogenic	0.8639	pathogenic	-2.701	Highly Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
L/C	0.9391	likely_pathogenic	0.9408	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.9989	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/E	0.9898	likely_pathogenic	0.991	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/F	0.5402	ambiguous	0.5951	pathogenic	-1.658	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
L/G	0.9822	likely_pathogenic	0.984	pathogenic	-3.312	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9783	likely_pathogenic	0.9826	pathogenic	-2.871	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/I	0.199	likely_benign	0.1926	benign	-0.901	Destabilizing	0.18	N	0.346	neutral	None	None	None	None	N
L/K	0.9863	likely_pathogenic	0.9881	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/M	0.2913	likely_benign	0.3189	benign	-0.972	Destabilizing	0.997	D	0.732	prob.delet.	D	0.52459341	None	None	N
L/N	0.9934	likely_pathogenic	0.9942	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/P	0.9903	likely_pathogenic	0.9911	pathogenic	-1.486	Destabilizing	1.0	D	0.863	deleterious	D	0.548231074	None	None	N
L/Q	0.9599	likely_pathogenic	0.9686	pathogenic	-2.32	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.548231074	None	None	N
L/R	0.9671	likely_pathogenic	0.9717	pathogenic	-1.931	Destabilizing	1.0	D	0.836	deleterious	D	0.536874768	None	None	N
L/S	0.9821	likely_pathogenic	0.9849	pathogenic	-3.301	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/T	0.9056	likely_pathogenic	0.9132	pathogenic	-2.845	Highly Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
L/V	0.2076	likely_benign	0.1996	benign	-1.486	Destabilizing	0.179	N	0.337	neutral	N	0.477136398	None	None	N
L/W	0.9055	likely_pathogenic	0.9282	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/Y	0.9345	likely_pathogenic	0.9503	pathogenic	-1.792	Destabilizing	0.998	D	0.789	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.