TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9621	29086;29087;29088	chr2:178707706;178707705;178707704	chr2:179572433;179572432;179572431
N2AB	9304	28135;28136;28137	chr2:178707706;178707705;178707704	chr2:179572433;179572432;179572431
N2A	8377	25354;25355;25356	chr2:178707706;178707705;178707704	chr2:179572433;179572432;179572431
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-82
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.151
• 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/N	None	None	0.994	None	0.856	0.785	0.909067042513	gnomAD-4.0.0	1.59103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85776E-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	0.9519	likely_pathogenic	0.9294	pathogenic	-2.14	Highly Destabilizing	0.845	D	0.725	prob.delet.	None	None	None	None	N
I/C	0.9562	likely_pathogenic	0.944	pathogenic	-1.214	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
I/D	0.998	likely_pathogenic	0.9962	pathogenic	-2.084	Highly Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
I/E	0.9924	likely_pathogenic	0.9877	pathogenic	-1.89	Destabilizing	0.987	D	0.862	deleterious	None	None	None	None	N
I/F	0.481	ambiguous	0.4081	ambiguous	-1.259	Destabilizing	0.967	D	0.723	prob.delet.	None	None	None	None	N
I/G	0.9879	likely_pathogenic	0.9806	pathogenic	-2.64	Highly Destabilizing	0.987	D	0.855	deleterious	None	None	None	None	N
I/H	0.9863	likely_pathogenic	0.9738	pathogenic	-1.953	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
I/K	0.9752	likely_pathogenic	0.9601	pathogenic	-1.491	Destabilizing	0.987	D	0.865	deleterious	None	None	None	None	N
I/L	0.3082	likely_benign	0.2778	benign	-0.721	Destabilizing	0.426	N	0.475	neutral	None	None	None	None	N
I/M	0.3196	likely_benign	0.2831	benign	-0.562	Destabilizing	0.983	D	0.686	prob.neutral	None	None	None	None	N
I/N	0.9626	likely_pathogenic	0.9362	pathogenic	-1.7	Destabilizing	0.994	D	0.856	deleterious	None	None	None	None	N
I/P	0.9801	likely_pathogenic	0.9679	pathogenic	-1.172	Destabilizing	0.996	D	0.86	deleterious	None	None	None	None	N
I/Q	0.9812	likely_pathogenic	0.9678	pathogenic	-1.616	Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
I/R	0.9709	likely_pathogenic	0.9515	pathogenic	-1.204	Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
I/S	0.9583	likely_pathogenic	0.9275	pathogenic	-2.393	Highly Destabilizing	0.983	D	0.822	deleterious	None	None	None	None	N
I/T	0.9221	likely_pathogenic	0.889	pathogenic	-2.054	Highly Destabilizing	0.892	D	0.771	deleterious	None	None	None	None	N
I/V	0.1557	likely_benign	0.1658	benign	-1.172	Destabilizing	0.011	N	0.212	neutral	None	None	None	None	N
I/W	0.9774	likely_pathogenic	0.9635	pathogenic	-1.567	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
I/Y	0.9199	likely_pathogenic	0.8869	pathogenic	-1.248	Destabilizing	0.987	D	0.747	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.