TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7348	22267;22268;22269	chr2:178722857;178722856;178722855	chr2:179587584;179587583;179587582
N2AB	7031	21316;21317;21318	chr2:178722857;178722856;178722855	chr2:179587584;179587583;179587582
N2A	6104	18535;18536;18537	chr2:178722857;178722856;178722855	chr2:179587584;179587583;179587582
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-58
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4029
• 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
G/E	None	None	0.998	D	0.559	0.712	0.774179987323	gnomAD-4.0.0	6.84505E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99692E-07	0	0
G/R	rs1273201877	-0.443	1.0	D	0.773	0.785	0.871131940551	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
G/A	0.6653	likely_pathogenic	0.7412	pathogenic	-0.438	Destabilizing	0.999	D	0.649	neutral	D	0.550695897	None	None	I
G/C	0.9594	likely_pathogenic	0.9764	pathogenic	-0.69	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/D	0.986	likely_pathogenic	0.9908	pathogenic	-0.843	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/E	0.986	likely_pathogenic	0.9921	pathogenic	-0.942	Destabilizing	0.998	D	0.559	neutral	D	0.585359869	None	None	I
G/F	0.9948	likely_pathogenic	0.9967	pathogenic	-0.912	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
G/H	0.9966	likely_pathogenic	0.9982	pathogenic	-1.013	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
G/I	0.9821	likely_pathogenic	0.9909	pathogenic	-0.27	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
G/K	0.9957	likely_pathogenic	0.9978	pathogenic	-1.14	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/L	0.9896	likely_pathogenic	0.994	pathogenic	-0.27	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/M	0.9927	likely_pathogenic	0.9955	pathogenic	-0.32	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
G/N	0.9903	likely_pathogenic	0.9936	pathogenic	-0.722	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/P	0.9982	likely_pathogenic	0.9985	pathogenic	-0.287	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/Q	0.9919	likely_pathogenic	0.9953	pathogenic	-0.923	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/R	0.9853	likely_pathogenic	0.9926	pathogenic	-0.783	Destabilizing	1.0	D	0.773	deleterious	D	0.630549818	None	None	I
G/S	0.7448	likely_pathogenic	0.8302	pathogenic	-0.875	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/T	0.9485	likely_pathogenic	0.9632	pathogenic	-0.901	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
G/V	0.9507	likely_pathogenic	0.9754	pathogenic	-0.287	Destabilizing	1.0	D	0.778	deleterious	D	0.621031068	None	None	I
G/W	0.9928	likely_pathogenic	0.9959	pathogenic	-1.239	Destabilizing	1.0	D	0.67	neutral	D	0.646972788	None	None	I
G/Y	0.9946	likely_pathogenic	0.997	pathogenic	-0.834	Destabilizing	1.0	D	0.759	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.