TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7750	23473;23474;23475	chr2:178720514;178720513;178720512	chr2:179585241;179585240;179585239
N2AB	7433	22522;22523;22524	chr2:178720514;178720513;178720512	chr2:179585241;179585240;179585239
N2A	6506	19741;19742;19743	chr2:178720514;178720513;178720512	chr2:179585241;179585240;179585239
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-62
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1584
• 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
I/V	None	None	None	N	0.125	0.145	0.349204839081	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8592E-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
I/A	0.5938	likely_pathogenic	0.6368	pathogenic	-2.261	Highly Destabilizing	0.291	N	0.387	neutral	None	None	None	None	N
I/C	0.8105	likely_pathogenic	0.8286	pathogenic	-1.644	Destabilizing	0.982	D	0.556	neutral	None	None	None	None	N
I/D	0.9275	likely_pathogenic	0.9407	pathogenic	-1.767	Destabilizing	0.934	D	0.644	neutral	None	None	None	None	N
I/E	0.8335	likely_pathogenic	0.851	pathogenic	-1.657	Destabilizing	0.913	D	0.627	neutral	None	None	None	None	N
I/F	0.2372	likely_benign	0.2789	benign	-1.497	Destabilizing	0.677	D	0.507	neutral	N	0.519015598	None	None	N
I/G	0.8449	likely_pathogenic	0.8734	pathogenic	-2.712	Highly Destabilizing	0.934	D	0.607	neutral	None	None	None	None	N
I/H	0.7706	likely_pathogenic	0.792	pathogenic	-1.945	Destabilizing	0.985	D	0.635	neutral	None	None	None	None	N
I/K	0.6984	likely_pathogenic	0.6977	pathogenic	-1.546	Destabilizing	0.294	N	0.631	neutral	None	None	None	None	N
I/L	0.1489	likely_benign	0.1591	benign	-1.024	Destabilizing	0.002	N	0.322	neutral	N	0.492405	None	None	N
I/M	0.109	likely_benign	0.1145	benign	-0.908	Destabilizing	0.386	N	0.527	neutral	D	0.523709342	None	None	N
I/N	0.5092	ambiguous	0.5352	ambiguous	-1.548	Destabilizing	0.97	D	0.645	neutral	N	0.511677986	None	None	N
I/P	0.9336	likely_pathogenic	0.9503	pathogenic	-1.41	Destabilizing	0.977	D	0.64	neutral	None	None	None	None	N
I/Q	0.677	likely_pathogenic	0.6979	pathogenic	-1.594	Destabilizing	0.947	D	0.654	neutral	None	None	None	None	N
I/R	0.6323	likely_pathogenic	0.6427	pathogenic	-1.085	Destabilizing	0.849	D	0.657	neutral	None	None	None	None	N
I/S	0.575	likely_pathogenic	0.6112	pathogenic	-2.328	Highly Destabilizing	0.6	D	0.545	neutral	N	0.506967498	None	None	N
I/T	0.4581	ambiguous	0.4854	ambiguous	-2.078	Highly Destabilizing	0.311	N	0.471	neutral	D	0.523672057	None	None	N
I/V	0.0873	likely_benign	0.0967	benign	-1.41	Destabilizing	None	N	0.125	neutral	N	0.492786215	None	None	N
I/W	0.8473	likely_pathogenic	0.8734	pathogenic	-1.66	Destabilizing	0.996	D	0.675	prob.neutral	None	None	None	None	N
I/Y	0.6267	likely_pathogenic	0.6385	pathogenic	-1.42	Destabilizing	0.397	N	0.585	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.