TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34182	102769;102770;102771	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
N2AB	32541	97846;97847;97848	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
N2A	31614	95065;95066;95067	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
N2B	25117	75574;75575;75576	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
Novex-1	25242	75949;75950;75951	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
Novex-2	25309	76150;76151;76152	chr2:178534071;178534070;178534069	chr2:179398798;179398797;179398796
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-160
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.1143
• 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
K/T	rs1348175807	-0.736	1.0	N	0.695	0.48	0.326074293725	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/T	rs1348175807	-0.736	1.0	N	0.695	0.48	0.326074293725	gnomAD-4.0.0	4.77303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57319E-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
K/A	0.8898	likely_pathogenic	0.9173	pathogenic	-0.568	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/C	0.9679	likely_pathogenic	0.9788	pathogenic	-0.515	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/D	0.8986	likely_pathogenic	0.9165	pathogenic	0.108	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/E	0.719	likely_pathogenic	0.7797	pathogenic	0.217	Stabilizing	0.999	D	0.494	neutral	N	0.515950211	None	None	N
K/F	0.976	likely_pathogenic	0.9813	pathogenic	-0.296	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
K/G	0.9187	likely_pathogenic	0.9399	pathogenic	-0.922	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/H	0.7162	likely_pathogenic	0.747	pathogenic	-1.209	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/I	0.8249	likely_pathogenic	0.8659	pathogenic	0.341	Stabilizing	1.0	D	0.671	neutral	N	0.464961732	None	None	N
K/L	0.8068	likely_pathogenic	0.8412	pathogenic	0.341	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/M	0.707	likely_pathogenic	0.7587	pathogenic	0.188	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	N
K/N	0.7908	likely_pathogenic	0.8342	pathogenic	-0.359	Destabilizing	1.0	D	0.656	neutral	N	0.45513591	None	None	N
K/P	0.9626	likely_pathogenic	0.9717	pathogenic	0.069	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/Q	0.5852	likely_pathogenic	0.6517	pathogenic	-0.4	Destabilizing	1.0	D	0.633	neutral	N	0.456403357	None	None	N
K/R	0.1834	likely_benign	0.2131	benign	-0.503	Destabilizing	0.999	D	0.498	neutral	N	0.449815645	None	None	N
K/S	0.9063	likely_pathogenic	0.9317	pathogenic	-1.036	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
K/T	0.6517	likely_pathogenic	0.7127	pathogenic	-0.717	Destabilizing	1.0	D	0.695	prob.neutral	N	0.455896378	None	None	N
K/V	0.8413	likely_pathogenic	0.8759	pathogenic	0.069	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/W	0.9733	likely_pathogenic	0.9803	pathogenic	-0.177	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
K/Y	0.8986	likely_pathogenic	0.9183	pathogenic	0.109	Stabilizing	1.0	D	0.635	neutral	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.