TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7613	23062;23063;23064	chr2:178721182;178721181;178721180	chr2:179585909;179585908;179585907
N2AB	7296	22111;22112;22113	chr2:178721182;178721181;178721180	chr2:179585909;179585908;179585907
N2A	6369	19330;19331;19332	chr2:178721182;178721181;178721180	chr2:179585909;179585908;179585907
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-61
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4598
• 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	rs1360753746	0.023	0.994	N	0.717	0.273	0.199424873507	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.77E-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
K/A	0.7194	likely_pathogenic	0.6322	pathogenic	-0.348	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
K/C	0.924	likely_pathogenic	0.8877	pathogenic	-0.434	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.8794	likely_pathogenic	0.8096	pathogenic	0.389	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/E	0.5622	ambiguous	0.45	ambiguous	0.47	Stabilizing	0.992	D	0.551	neutral	N	0.502095479	None	None	N
K/F	0.9195	likely_pathogenic	0.8877	pathogenic	-0.232	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/G	0.7618	likely_pathogenic	0.6953	pathogenic	-0.638	Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	N
K/H	0.5445	ambiguous	0.4875	ambiguous	-0.781	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/I	0.6914	likely_pathogenic	0.6197	pathogenic	0.369	Stabilizing	0.977	D	0.789	deleterious	N	0.460099887	None	None	N
K/L	0.6408	likely_pathogenic	0.55	ambiguous	0.369	Stabilizing	0.941	D	0.694	prob.neutral	None	None	None	None	N
K/M	0.4628	ambiguous	0.354	ambiguous	0.047	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
K/N	0.7315	likely_pathogenic	0.6348	pathogenic	-0.013	Destabilizing	0.999	D	0.729	prob.delet.	N	0.457867707	None	None	N
K/P	0.6811	likely_pathogenic	0.614	pathogenic	0.159	Stabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
K/Q	0.2841	likely_benign	0.2433	benign	-0.065	Destabilizing	0.994	D	0.717	prob.delet.	N	0.483472433	None	None	N
K/R	0.1128	likely_benign	0.1181	benign	-0.145	Destabilizing	0.987	D	0.492	neutral	N	0.467233544	None	None	N
K/S	0.7849	likely_pathogenic	0.7018	pathogenic	-0.662	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	N
K/T	0.4867	ambiguous	0.3903	ambiguous	-0.387	Destabilizing	0.998	D	0.753	deleterious	N	0.49128384	None	None	N
K/V	0.6639	likely_pathogenic	0.5971	pathogenic	0.159	Stabilizing	0.987	D	0.712	prob.delet.	None	None	None	None	N
K/W	0.9024	likely_pathogenic	0.8852	pathogenic	-0.155	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Y	0.7973	likely_pathogenic	0.7499	pathogenic	0.151	Stabilizing	0.989	D	0.78	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.