TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20059	60400;60401;60402	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
N2AB	18418	55477;55478;55479	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
N2A	17491	52696;52697;52698	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
N2B	10994	33205;33206;33207	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
Novex-1	11119	33580;33581;33582	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
Novex-2	11186	33781;33782;33783	chr2:178591644;178591643;178591642	chr2:179456371;179456370;179456369
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-33
• Domain position: 83
• Structural Position: 118
• Q(SASA): 0.1208
• 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
G/R	rs778467153	None	0.497	N	0.799	0.333	0.376216005999	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85989E-06	0	0
G/S	None	-1.179	None	N	0.441	0.217	0.0297737177859	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
G/S	None	-1.179	None	N	0.441	0.217	0.0297737177859	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85989E-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
G/A	0.2686	likely_benign	0.3009	benign	-0.863	Destabilizing	0.055	N	0.735	prob.delet.	N	0.520768295	None	None	N
G/C	0.495	ambiguous	0.5488	ambiguous	-0.948	Destabilizing	0.883	D	0.848	deleterious	D	0.533899027	None	None	N
G/D	0.9276	likely_pathogenic	0.9427	pathogenic	-1.626	Destabilizing	0.001	N	0.637	neutral	N	0.521528764	None	None	N
G/E	0.9626	likely_pathogenic	0.9642	pathogenic	-1.642	Destabilizing	0.157	N	0.787	deleterious	None	None	None	None	N
G/F	0.986	likely_pathogenic	0.9863	pathogenic	-0.998	Destabilizing	0.726	D	0.852	deleterious	None	None	None	None	N
G/H	0.9529	likely_pathogenic	0.9578	pathogenic	-1.573	Destabilizing	0.909	D	0.797	deleterious	None	None	None	None	N
G/I	0.9448	likely_pathogenic	0.9536	pathogenic	-0.355	Destabilizing	0.567	D	0.845	deleterious	None	None	None	None	N
G/K	0.9934	likely_pathogenic	0.9932	pathogenic	-1.448	Destabilizing	0.396	N	0.803	deleterious	None	None	None	None	N
G/L	0.9345	likely_pathogenic	0.9446	pathogenic	-0.355	Destabilizing	0.567	D	0.848	deleterious	None	None	None	None	N
G/M	0.9443	likely_pathogenic	0.9515	pathogenic	-0.319	Destabilizing	0.968	D	0.845	deleterious	None	None	None	None	N
G/N	0.887	likely_pathogenic	0.9144	pathogenic	-1.164	Destabilizing	0.157	N	0.751	deleterious	None	None	None	None	N
G/P	0.9935	likely_pathogenic	0.9934	pathogenic	-0.484	Destabilizing	0.567	D	0.805	deleterious	None	None	None	None	N
G/Q	0.9653	likely_pathogenic	0.9648	pathogenic	-1.305	Destabilizing	0.567	D	0.798	deleterious	None	None	None	None	N
G/R	0.9773	likely_pathogenic	0.9773	pathogenic	-1.158	Destabilizing	0.497	N	0.799	deleterious	N	0.521782253	None	None	N
G/S	0.0796	likely_benign	0.0985	benign	-1.406	Destabilizing	None	N	0.441	neutral	N	0.412106272	None	None	N
G/T	0.5363	ambiguous	0.5806	pathogenic	-1.351	Destabilizing	0.157	N	0.787	deleterious	None	None	None	None	N
G/V	0.8785	likely_pathogenic	0.8956	pathogenic	-0.484	Destabilizing	0.497	N	0.851	deleterious	D	0.533392048	None	None	N
G/W	0.9713	likely_pathogenic	0.9703	pathogenic	-1.452	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
G/Y	0.9664	likely_pathogenic	0.9699	pathogenic	-1.034	Destabilizing	0.726	D	0.847	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.