TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20611	62056;62057;62058	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
N2AB	18970	57133;57134;57135	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
N2A	18043	54352;54353;54354	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
N2B	11546	34861;34862;34863	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
Novex-1	11671	35236;35237;35238	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
Novex-2	11738	35437;35438;35439	chr2:178589894;178589893;178589892	chr2:179454621;179454620;179454619
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-37
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.1872
• 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
P/S	None	None	1.0	N	0.765	0.348	0.318540980066	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05

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
P/A	0.1614	likely_benign	0.1793	benign	-1.493	Destabilizing	1.0	D	0.708	prob.delet.	N	0.454928756	None	None	N
P/C	0.8309	likely_pathogenic	0.8517	pathogenic	-0.765	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
P/D	0.9005	likely_pathogenic	0.9076	pathogenic	-1.408	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/E	0.7366	likely_pathogenic	0.7415	pathogenic	-1.399	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/F	0.9137	likely_pathogenic	0.9222	pathogenic	-1.132	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
P/G	0.632	likely_pathogenic	0.661	pathogenic	-1.815	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/H	0.6979	likely_pathogenic	0.7107	pathogenic	-1.348	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
P/I	0.5798	likely_pathogenic	0.6234	pathogenic	-0.702	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
P/K	0.7396	likely_pathogenic	0.7325	pathogenic	-1.254	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/L	0.3999	ambiguous	0.4283	ambiguous	-0.702	Destabilizing	1.0	D	0.742	deleterious	N	0.490465481	None	None	N
P/M	0.6579	likely_pathogenic	0.6959	pathogenic	-0.463	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/N	0.774	likely_pathogenic	0.8028	pathogenic	-0.982	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/Q	0.5399	ambiguous	0.5521	ambiguous	-1.148	Destabilizing	1.0	D	0.741	deleterious	N	0.503029347	None	None	N
P/R	0.6605	likely_pathogenic	0.6379	pathogenic	-0.708	Destabilizing	1.0	D	0.744	deleterious	N	0.511360828	None	None	N
P/S	0.4209	ambiguous	0.4273	ambiguous	-1.46	Destabilizing	1.0	D	0.765	deleterious	N	0.455102114	None	None	N
P/T	0.3026	likely_benign	0.3284	benign	-1.347	Destabilizing	1.0	D	0.761	deleterious	N	0.423952488	None	None	N
P/V	0.4107	ambiguous	0.4518	ambiguous	-0.932	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
P/W	0.9625	likely_pathogenic	0.9638	pathogenic	-1.353	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
P/Y	0.8769	likely_pathogenic	0.8934	pathogenic	-1.069	Destabilizing	1.0	D	0.683	prob.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.