TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9089	27490;27491;27492	chr2:178712760;178712759;178712758	chr2:179577487;179577486;179577485
N2AB	8772	26539;26540;26541	chr2:178712760;178712759;178712758	chr2:179577487;179577486;179577485
N2A	7845	23758;23759;23760	chr2:178712760;178712759;178712758	chr2:179577487;179577486;179577485
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: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-76
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.097
• 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	rs794729633	-2.299	1.0	D	0.793	0.807	0.756873525501	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/H	rs794729633	-2.299	1.0	D	0.793	0.807	0.756873525501	gnomAD-4.0.0	1.16316E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52909E-05	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
Y/A	0.9912	likely_pathogenic	0.9933	pathogenic	-1.999	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/C	0.9373	likely_pathogenic	0.9474	pathogenic	-1.471	Destabilizing	1.0	D	0.876	deleterious	D	0.666424616	None	None	N
Y/D	0.9927	likely_pathogenic	0.9963	pathogenic	-2.605	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.666424616	None	None	N
Y/E	0.9967	likely_pathogenic	0.9981	pathogenic	-2.35	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/F	0.2091	likely_benign	0.2087	benign	-0.604	Destabilizing	0.999	D	0.696	prob.neutral	D	0.604538454	None	None	N
Y/G	0.9847	likely_pathogenic	0.9891	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/H	0.9655	likely_pathogenic	0.9786	pathogenic	-1.975	Destabilizing	1.0	D	0.793	deleterious	D	0.666222812	None	None	N
Y/I	0.8365	likely_pathogenic	0.8141	pathogenic	-0.494	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/K	0.9964	likely_pathogenic	0.9981	pathogenic	-1.668	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.8256	likely_pathogenic	0.8287	pathogenic	-0.494	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
Y/M	0.9306	likely_pathogenic	0.9356	pathogenic	-0.685	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/N	0.9509	likely_pathogenic	0.9707	pathogenic	-2.573	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.666424616	None	None	N
Y/P	0.9985	likely_pathogenic	0.999	pathogenic	-1.011	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.9966	likely_pathogenic	0.998	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/R	0.9924	likely_pathogenic	0.9954	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.9854	likely_pathogenic	0.9905	pathogenic	-2.888	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.666424616	None	None	N
Y/T	0.9907	likely_pathogenic	0.9929	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.8182	likely_pathogenic	0.7817	pathogenic	-1.011	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/W	0.8416	likely_pathogenic	0.8574	pathogenic	0.022	Stabilizing	1.0	D	0.787	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.