TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14105	42538;42539;42540	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
N2AB	12464	37615;37616;37617	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
N2A	11537	34834;34835;34836	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
N2B	5040	15343;15344;15345	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
Novex-1	5165	15718;15719;15720	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
Novex-2	5232	15919;15920;15921	chr2:178634468;178634467;178634466	chr2:179499195;179499194;179499193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-91
• Domain position: 52
• Structural Position: 134
• Q(SASA): 0.6181
• 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/N	None	None	0.606	N	0.273	0.214	0.272205846399	gnomAD-4.0.0	6.84438E-07	None	None	None	None	N	None	0	0	None	0	2.52461E-05	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	0.8334	likely_pathogenic	0.8692	pathogenic	-0.498	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	N
K/C	0.9242	likely_pathogenic	0.9351	pathogenic	-0.586	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.9096	likely_pathogenic	0.915	pathogenic	-0.099	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	N
K/E	0.6538	likely_pathogenic	0.6513	pathogenic	0.001	Stabilizing	0.98	D	0.639	neutral	N	0.507134781	None	None	N
K/F	0.9605	likely_pathogenic	0.9697	pathogenic	-0.19	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
K/G	0.8286	likely_pathogenic	0.8499	pathogenic	-0.857	Destabilizing	0.985	D	0.649	neutral	None	None	None	None	N
K/H	0.7158	likely_pathogenic	0.7148	pathogenic	-1.17	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/I	0.8096	likely_pathogenic	0.8492	pathogenic	0.425	Stabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
K/L	0.7244	likely_pathogenic	0.7768	pathogenic	0.425	Stabilizing	0.171	N	0.445	neutral	None	None	None	None	N
K/M	0.5925	likely_pathogenic	0.6028	pathogenic	0.275	Stabilizing	0.994	D	0.658	neutral	D	0.592785735	None	None	N
K/N	0.7531	likely_pathogenic	0.7769	pathogenic	-0.457	Destabilizing	0.606	D	0.273	neutral	N	0.509286937	None	None	N
K/P	0.8989	likely_pathogenic	0.9347	pathogenic	0.148	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
K/Q	0.3747	ambiguous	0.3508	ambiguous	-0.546	Destabilizing	0.997	D	0.649	neutral	N	0.510047206	None	None	N
K/R	0.1395	likely_benign	0.1343	benign	-0.607	Destabilizing	0.99	D	0.579	neutral	N	0.495392752	None	None	N
K/S	0.838	likely_pathogenic	0.8603	pathogenic	-1.11	Destabilizing	0.985	D	0.616	neutral	None	None	None	None	N
K/T	0.5579	ambiguous	0.5867	pathogenic	-0.81	Destabilizing	0.98	D	0.63	neutral	N	0.507334499	None	None	N
K/V	0.7816	likely_pathogenic	0.8278	pathogenic	0.148	Stabilizing	0.971	D	0.637	neutral	None	None	None	None	N
K/W	0.9567	likely_pathogenic	0.9549	pathogenic	-0.065	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/Y	0.9102	likely_pathogenic	0.9165	pathogenic	0.223	Stabilizing	0.999	D	0.711	prob.delet.	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.