TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7114	21565;21566;21567	chr2:178723919;178723918;178723917	chr2:179588646;179588645;179588644
N2AB	6797	20614;20615;20616	chr2:178723919;178723918;178723917	chr2:179588646;179588645;179588644
N2A	5870	17833;17834;17835	chr2:178723919;178723918;178723917	chr2:179588646;179588645;179588644
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-55
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1019
• 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
Y/H	rs754909782	-2.887	1.0	D	0.789	0.765	0.770276685214	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.3077E-04	None	0	0	0
Y/H	rs754909782	-2.887	1.0	D	0.789	0.765	0.770276685214	gnomAD-4.0.0	3.42176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.79791E-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
Y/A	0.9788	likely_pathogenic	0.9734	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/C	0.782	likely_pathogenic	0.7445	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.671067909	None	None	N
Y/D	0.9901	likely_pathogenic	0.9886	pathogenic	-3.575	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.671067909	None	None	N
Y/E	0.9965	likely_pathogenic	0.9959	pathogenic	-3.341	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/F	0.1304	likely_benign	0.1223	benign	-1.052	Destabilizing	0.999	D	0.681	prob.neutral	D	0.564838298	None	None	N
Y/G	0.9752	likely_pathogenic	0.9723	pathogenic	-3.188	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/H	0.9076	likely_pathogenic	0.9033	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.670866105	None	None	N
Y/I	0.7587	likely_pathogenic	0.7063	pathogenic	-1.251	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/K	0.9942	likely_pathogenic	0.9937	pathogenic	-2.333	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/L	0.7387	likely_pathogenic	0.7056	pathogenic	-1.251	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
Y/M	0.9315	likely_pathogenic	0.9176	pathogenic	-1.326	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/N	0.9506	likely_pathogenic	0.9445	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.671067909	None	None	N
Y/P	0.9956	likely_pathogenic	0.995	pathogenic	-1.766	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/Q	0.9924	likely_pathogenic	0.9912	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/R	0.9796	likely_pathogenic	0.9784	pathogenic	-2.401	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.9508	likely_pathogenic	0.9451	pathogenic	-3.572	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.671067909	None	None	N
Y/T	0.9727	likely_pathogenic	0.966	pathogenic	-3.196	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/V	0.6945	likely_pathogenic	0.6306	pathogenic	-1.766	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/W	0.7897	likely_pathogenic	0.7768	pathogenic	-0.449	Destabilizing	1.0	D	0.784	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.