TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9671	29236;29237;29238	chr2:178707556;178707555;178707554	chr2:179572283;179572282;179572281
N2AB	9354	28285;28286;28287	chr2:178707556;178707555;178707554	chr2:179572283;179572282;179572281
N2A	8427	25504;25505;25506	chr2:178707556;178707555;178707554	chr2:179572283;179572282;179572281
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-82
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1896
• Predicted PPI site: I

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
D/G	rs530627450	-1.279	0.989	None	0.683	0.532	0.440498838766	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
D/G	rs530627450	-1.279	0.989	None	0.683	0.532	0.440498838766	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
D/G	rs530627450	-1.279	0.989	None	0.683	0.532	0.440498838766	gnomAD-4.0.0	6.56435E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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
D/A	0.3488	ambiguous	0.2512	benign	-0.738	Destabilizing	0.977	D	0.727	prob.delet.	None	None	None	None	I
D/C	0.9011	likely_pathogenic	0.8283	pathogenic	-0.252	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
D/E	0.3769	ambiguous	0.2959	benign	-0.638	Destabilizing	0.117	N	0.25	neutral	None	None	None	None	I
D/F	0.8996	likely_pathogenic	0.8325	pathogenic	-0.264	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
D/G	0.4497	ambiguous	0.3379	benign	-1.107	Destabilizing	0.989	D	0.683	prob.neutral	None	None	None	None	I
D/H	0.7074	likely_pathogenic	0.5893	pathogenic	-0.53	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
D/I	0.8224	likely_pathogenic	0.6997	pathogenic	0.249	Stabilizing	0.998	D	0.853	deleterious	None	None	None	None	I
D/K	0.8038	likely_pathogenic	0.7201	pathogenic	-0.347	Destabilizing	0.99	D	0.715	prob.delet.	None	None	None	None	I
D/L	0.835	likely_pathogenic	0.7367	pathogenic	0.249	Stabilizing	0.995	D	0.83	deleterious	None	None	None	None	I
D/M	0.9231	likely_pathogenic	0.8659	pathogenic	0.736	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
D/N	0.2194	likely_benign	0.1702	benign	-0.821	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	I
D/P	0.9931	likely_pathogenic	0.9845	pathogenic	-0.055	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	I
D/Q	0.712	likely_pathogenic	0.6239	pathogenic	-0.684	Destabilizing	0.99	D	0.755	deleterious	None	None	None	None	I
D/R	0.8296	likely_pathogenic	0.7466	pathogenic	-0.172	Destabilizing	0.995	D	0.828	deleterious	None	None	None	None	I
D/S	0.2431	likely_benign	0.1933	benign	-1.133	Destabilizing	0.983	D	0.644	neutral	None	None	None	None	I
D/T	0.581	likely_pathogenic	0.4732	ambiguous	-0.822	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	I
D/V	0.6121	likely_pathogenic	0.4656	ambiguous	-0.055	Destabilizing	0.997	D	0.821	deleterious	None	None	None	None	I
D/W	0.9906	likely_pathogenic	0.9822	pathogenic	-0.021	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
D/Y	0.6603	likely_pathogenic	0.5453	ambiguous	0.014	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I

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.