TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16128	48607;48608;48609	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
N2AB	14487	43684;43685;43686	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
N2A	13560	40903;40904;40905	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
N2B	7063	21412;21413;21414	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
Novex-1	7188	21787;21788;21789	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
Novex-2	7255	21988;21989;21990	chr2:178615719;178615718;178615717	chr2:179480446;179480445;179480444
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: Fn3-4
• Domain position: 74
• Structural Position: 107
• Q(SASA): 0.0871
• 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/E	None	None	0.896	N	0.668	0.275	0.264547087235	gnomAD-4.0.0	1.59428E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43402E-05	0
K/T	None	None	0.946	N	0.606	0.275	0.288727942641	gnomAD-4.0.0	3.18852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72889E-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	0.69	likely_pathogenic	0.726	pathogenic	-1.299	Destabilizing	0.919	D	0.635	neutral	None	None	None	None	N
K/C	0.7141	likely_pathogenic	0.7413	pathogenic	-1.423	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
K/D	0.9763	likely_pathogenic	0.9811	pathogenic	-2.086	Highly Destabilizing	0.988	D	0.624	neutral	None	None	None	None	N
K/E	0.684	likely_pathogenic	0.7284	pathogenic	-1.789	Destabilizing	0.896	D	0.668	neutral	N	0.479874733	None	None	N
K/F	0.9561	likely_pathogenic	0.9654	pathogenic	-0.424	Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
K/G	0.8176	likely_pathogenic	0.8498	pathogenic	-1.779	Destabilizing	0.959	D	0.631	neutral	None	None	None	None	N
K/H	0.4865	ambiguous	0.5099	ambiguous	-1.805	Destabilizing	0.988	D	0.717	prob.delet.	None	None	None	None	N
K/I	0.7477	likely_pathogenic	0.8065	pathogenic	0.065	Stabilizing	0.984	D	0.807	deleterious	N	0.484722186	None	None	N
K/L	0.6535	likely_pathogenic	0.7183	pathogenic	0.065	Stabilizing	0.919	D	0.631	neutral	None	None	None	None	N
K/M	0.4767	ambiguous	0.5462	ambiguous	-0.343	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/N	0.8813	likely_pathogenic	0.8947	pathogenic	-2.022	Highly Destabilizing	0.896	D	0.567	neutral	N	0.499503292	None	None	N
K/P	0.9958	likely_pathogenic	0.9971	pathogenic	-0.37	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
K/Q	0.2484	likely_benign	0.2637	benign	-1.6	Destabilizing	0.896	D	0.585	neutral	N	0.472229913	None	None	N
K/R	0.074	likely_benign	0.0716	benign	-1.315	Destabilizing	0.011	N	0.263	neutral	N	0.305224039	None	None	N
K/S	0.7317	likely_pathogenic	0.7554	pathogenic	-2.426	Highly Destabilizing	0.919	D	0.627	neutral	None	None	None	None	N
K/T	0.5118	ambiguous	0.5961	pathogenic	-1.888	Destabilizing	0.946	D	0.606	neutral	N	0.470662552	None	None	N
K/V	0.6704	likely_pathogenic	0.7402	pathogenic	-0.37	Destabilizing	0.988	D	0.655	neutral	None	None	None	None	N
K/W	0.9212	likely_pathogenic	0.9359	pathogenic	-0.626	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/Y	0.8435	likely_pathogenic	0.8678	pathogenic	-0.26	Destabilizing	0.996	D	0.767	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.