TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14404	43435;43436;43437	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
N2AB	12763	38512;38513;38514	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
N2A	11836	35731;35732;35733	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
N2B	5339	16240;16241;16242	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
Novex-1	5464	16615;16616;16617	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
Novex-2	5531	16816;16817;16818	chr2:178632921;178632920;178632919	chr2:179497648;179497647;179497646
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-94
• Domain position: 86
• Structural Position: 177
• Q(SASA): 0.1254
• 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/Q	None	None	0.999	N	0.821	0.232	0.219573609325	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
K/T	rs1296402152	-0.955	0.999	N	0.749	0.427	0.265010934533	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/T	rs1296402152	-0.955	0.999	N	0.749	0.427	0.265010934533	gnomAD-4.0.0	1.5937E-06	None	None	None	None	N	None	0	2.29064E-05	None	0	0	None	0	0	0	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	0.7672	likely_pathogenic	0.7448	pathogenic	-0.584	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
K/C	0.9257	likely_pathogenic	0.9112	pathogenic	-0.683	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/D	0.91	likely_pathogenic	0.8971	pathogenic	-0.183	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
K/E	0.4022	ambiguous	0.379	ambiguous	-0.037	Destabilizing	0.997	D	0.735	deleterious	N	0.434762658	None	None	N
K/F	0.9621	likely_pathogenic	0.9498	pathogenic	-0.18	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/G	0.8456	likely_pathogenic	0.8377	pathogenic	-0.948	Destabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
K/H	0.6422	likely_pathogenic	0.5888	pathogenic	-0.969	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/I	0.7171	likely_pathogenic	0.6699	pathogenic	0.366	Stabilizing	0.999	D	0.805	deleterious	N	0.463365763	None	None	N
K/L	0.7238	likely_pathogenic	0.6819	pathogenic	0.366	Stabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
K/M	0.5262	ambiguous	0.492	ambiguous	-0.045	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/N	0.7917	likely_pathogenic	0.7538	pathogenic	-0.65	Destabilizing	0.999	D	0.793	deleterious	D	0.557990936	None	None	N
K/P	0.9781	likely_pathogenic	0.9761	pathogenic	0.077	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
K/Q	0.2994	likely_benign	0.2778	benign	-0.582	Destabilizing	0.999	D	0.821	deleterious	N	0.424369624	None	None	N
K/R	0.122	likely_benign	0.1172	benign	-0.463	Destabilizing	0.997	D	0.664	prob.neutral	N	0.432205437	None	None	N
K/S	0.7886	likely_pathogenic	0.7642	pathogenic	-1.229	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
K/T	0.4349	ambiguous	0.4172	ambiguous	-0.873	Destabilizing	0.999	D	0.749	deleterious	N	0.423706473	None	None	N
K/V	0.687	likely_pathogenic	0.6516	pathogenic	0.077	Stabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/W	0.942	likely_pathogenic	0.9244	pathogenic	-0.136	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/Y	0.9191	likely_pathogenic	0.8988	pathogenic	0.144	Stabilizing	1.0	D	0.808	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.