TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8689	26290;26291;26292	chr2:178715121;178715120;178715119	chr2:179579848;179579847;179579846
N2AB	8372	25339;25340;25341	chr2:178715121;178715120;178715119	chr2:179579848;179579847;179579846
N2A	7445	22558;22559;22560	chr2:178715121;178715120;178715119	chr2:179579848;179579847;179579846
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-72
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1773
• 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
Y/C	None	None	1.0	D	0.755	0.578	0.762425462539	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9245	likely_pathogenic	0.9145	pathogenic	-2.882	Highly Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
Y/C	0.3987	ambiguous	0.3863	ambiguous	-1.855	Destabilizing	1.0	D	0.755	deleterious	D	0.524805037	None	None	N
Y/D	0.9395	likely_pathogenic	0.9211	pathogenic	-2.538	Highly Destabilizing	1.0	D	0.798	deleterious	D	0.548024626	None	None	N
Y/E	0.9639	likely_pathogenic	0.955	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
Y/F	0.149	likely_benign	0.1358	benign	-1.035	Destabilizing	0.113	N	0.322	neutral	N	0.479667776	None	None	N
Y/G	0.8868	likely_pathogenic	0.8778	pathogenic	-3.306	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Y/H	0.5253	ambiguous	0.4773	ambiguous	-1.793	Destabilizing	1.0	D	0.725	prob.delet.	D	0.529365878	None	None	N
Y/I	0.7342	likely_pathogenic	0.709	pathogenic	-1.508	Destabilizing	0.969	D	0.709	prob.delet.	None	None	None	None	N
Y/K	0.9594	likely_pathogenic	0.9477	pathogenic	-2.134	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/L	0.7422	likely_pathogenic	0.7354	pathogenic	-1.508	Destabilizing	0.898	D	0.491	neutral	None	None	None	None	N
Y/M	0.8116	likely_pathogenic	0.8089	pathogenic	-1.296	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
Y/N	0.6269	likely_pathogenic	0.5957	pathogenic	-2.825	Highly Destabilizing	1.0	D	0.78	deleterious	D	0.525058526	None	None	N
Y/P	0.9927	likely_pathogenic	0.9919	pathogenic	-1.975	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
Y/Q	0.8855	likely_pathogenic	0.8676	pathogenic	-2.562	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
Y/R	0.8943	likely_pathogenic	0.8706	pathogenic	-1.884	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/S	0.7939	likely_pathogenic	0.7687	pathogenic	-3.308	Highly Destabilizing	1.0	D	0.741	deleterious	N	0.501420863	None	None	N
Y/T	0.8824	likely_pathogenic	0.8665	pathogenic	-2.994	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
Y/V	0.6509	likely_pathogenic	0.6311	pathogenic	-1.975	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
Y/W	0.575	likely_pathogenic	0.5564	ambiguous	-0.394	Destabilizing	1.0	D	0.707	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.