TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9092	27499;27500;27501	chr2:178712751;178712750;178712749	chr2:179577478;179577477;179577476
N2AB	8775	26548;26549;26550	chr2:178712751;178712750;178712749	chr2:179577478;179577477;179577476
N2A	7848	23767;23768;23769	chr2:178712751;178712750;178712749	chr2:179577478;179577477;179577476
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: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-76
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.1499
• 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/R	None	None	0.061	N	0.529	0.292	0.663816143375	gnomAD-4.0.0	3.42104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49729E-06	0	0
I/V	rs1222539429	-0.876	None	N	0.174	0.103	0.517983797298	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/V	rs1222539429	-0.876	None	N	0.174	0.103	0.517983797298	gnomAD-4.0.0	8.21051E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	5.03905E-05	None	0	0	8.09514E-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	0.1657	likely_benign	0.1832	benign	-2.013	Highly Destabilizing	0.036	N	0.343	neutral	None	None	None	None	N
I/C	0.5758	likely_pathogenic	0.6024	pathogenic	-1.227	Destabilizing	0.749	D	0.517	neutral	None	None	None	None	N
I/D	0.4684	ambiguous	0.529	ambiguous	-1.708	Destabilizing	0.08	N	0.513	neutral	None	None	None	None	N
I/E	0.3083	likely_benign	0.3394	benign	-1.552	Destabilizing	0.001	N	0.471	neutral	None	None	None	None	N
I/F	0.1159	likely_benign	0.1205	benign	-1.212	Destabilizing	0.296	N	0.543	neutral	None	None	None	None	N
I/G	0.5061	ambiguous	0.563	ambiguous	-2.47	Highly Destabilizing	0.148	N	0.511	neutral	None	None	None	None	N
I/H	0.2764	likely_benign	0.3065	benign	-1.86	Destabilizing	0.001	N	0.463	neutral	None	None	None	None	N
I/K	0.2144	likely_benign	0.2397	benign	-1.172	Destabilizing	0.061	N	0.507	neutral	N	0.418365815	None	None	N
I/L	0.0885	likely_benign	0.0951	benign	-0.739	Destabilizing	0.028	N	0.354	neutral	N	0.410287836	None	None	N
I/M	0.0761	likely_benign	0.0793	benign	-0.717	Destabilizing	0.526	D	0.542	neutral	N	0.469701499	None	None	N
I/N	0.1845	likely_benign	0.2241	benign	-1.287	Destabilizing	0.148	N	0.533	neutral	None	None	None	None	N
I/P	0.926	likely_pathogenic	0.9403	pathogenic	-1.14	Destabilizing	0.46	N	0.595	neutral	None	None	None	None	N
I/Q	0.2288	likely_benign	0.26	benign	-1.255	Destabilizing	0.001	N	0.467	neutral	None	None	None	None	N
I/R	0.1463	likely_benign	0.1654	benign	-0.894	Destabilizing	0.061	N	0.529	neutral	N	0.439781237	None	None	N
I/S	0.167	likely_benign	0.1914	benign	-2.016	Highly Destabilizing	0.148	N	0.491	neutral	None	None	None	None	N
I/T	0.0944	likely_benign	0.1001	benign	-1.731	Destabilizing	0.116	N	0.446	neutral	N	0.421387477	None	None	N
I/V	0.0614	likely_benign	0.0624	benign	-1.14	Destabilizing	None	N	0.174	neutral	N	0.403609793	None	None	N
I/W	0.5792	likely_pathogenic	0.6109	pathogenic	-1.484	Destabilizing	0.972	D	0.581	neutral	None	None	None	None	N
I/Y	0.3713	ambiguous	0.4031	ambiguous	-1.176	Destabilizing	0.296	N	0.555	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.