TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8053	24382;24383;24384	chr2:178719233;178719232;178719231	chr2:179583960;179583959;179583958
N2AB	7736	23431;23432;23433	chr2:178719233;178719232;178719231	chr2:179583960;179583959;179583958
N2A	6809	20650;20651;20652	chr2:178719233;178719232;178719231	chr2:179583960;179583959;179583958
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: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-65
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.143
• 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/S	rs374167223	-0.954	1.0	D	0.825	0.635	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	2.9E-05	None	0	5.57E-05	None	0	None	0	4.45E-05	0
G/S	rs374167223	-0.954	1.0	D	0.825	0.635	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.0292E-04	0	0
G/S	rs374167223	-0.954	1.0	D	0.825	0.635	None	gnomAD-4.0.0	2.91261E-05	None	None	None	None	I	None	0	1.66694E-05	None	0	4.45653E-05	None	0	1.64582E-04	3.47527E-05	0	3.20205E-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
G/A	0.2244	likely_benign	0.2432	benign	-0.709	Destabilizing	1.0	D	0.745	deleterious	D	0.57261225	None	None	I
G/C	0.5449	ambiguous	0.5133	ambiguous	-0.951	Destabilizing	1.0	D	0.774	deleterious	D	0.662267089	None	None	I
G/D	0.557	ambiguous	0.5762	pathogenic	-1.15	Destabilizing	1.0	D	0.815	deleterious	D	0.613573233	None	None	I
G/E	0.6264	likely_pathogenic	0.6622	pathogenic	-1.156	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/F	0.9124	likely_pathogenic	0.9231	pathogenic	-0.968	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/H	0.743	likely_pathogenic	0.7787	pathogenic	-1.415	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
G/I	0.8389	likely_pathogenic	0.8636	pathogenic	-0.168	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/K	0.6816	likely_pathogenic	0.7236	pathogenic	-1.106	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/L	0.818	likely_pathogenic	0.8469	pathogenic	-0.168	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/M	0.8447	likely_pathogenic	0.8715	pathogenic	-0.191	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
G/N	0.5705	likely_pathogenic	0.6155	pathogenic	-0.918	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/P	0.9892	likely_pathogenic	0.9883	pathogenic	-0.306	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/Q	0.6488	likely_pathogenic	0.687	pathogenic	-1.015	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/R	0.5085	ambiguous	0.5562	ambiguous	-0.932	Destabilizing	1.0	D	0.829	deleterious	D	0.662065285	None	None	I
G/S	0.1675	likely_benign	0.1867	benign	-1.253	Destabilizing	1.0	D	0.825	deleterious	D	0.645642315	None	None	I
G/T	0.5252	ambiguous	0.573	pathogenic	-1.166	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/V	0.6942	likely_pathogenic	0.7183	pathogenic	-0.306	Destabilizing	1.0	D	0.825	deleterious	D	0.662267089	None	None	I
G/W	0.866	likely_pathogenic	0.8734	pathogenic	-1.419	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
G/Y	0.8447	likely_pathogenic	0.8595	pathogenic	-0.941	Destabilizing	1.0	D	0.781	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.