TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6082	18469;18470;18471	chr2:178730156;178730155;178730154	chr2:179594883;179594882;179594881
N2AB	5765	17518;17519;17520	chr2:178730156;178730155;178730154	chr2:179594883;179594882;179594881
N2A	4838	14737;14738;14739	chr2:178730156;178730155;178730154	chr2:179594883;179594882;179594881
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-44
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1249
• 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/H	None	None	1.0	D	0.788	0.87	0.763028283385	gnomAD-4.0.0	6.84412E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99596E-07	0	0
Y/N	rs777671590	-3.063	1.0	D	0.897	0.891	0.924445015539	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
Y/N	rs777671590	-3.063	1.0	D	0.897	0.891	0.924445015539	gnomAD-4.0.0	2.05324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69879E-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	0.9881	likely_pathogenic	0.9874	pathogenic	-2.254	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/C	0.8739	likely_pathogenic	0.849	pathogenic	-1.725	Destabilizing	1.0	D	0.89	deleterious	D	0.629510437	None	None	N
Y/D	0.9952	likely_pathogenic	0.9953	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.645529798	None	None	N
Y/E	0.9977	likely_pathogenic	0.9977	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.1401	likely_benign	0.1329	benign	-0.743	Destabilizing	0.999	D	0.673	neutral	D	0.5838758	None	None	N
Y/G	0.9863	likely_pathogenic	0.987	pathogenic	-2.712	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
Y/H	0.9494	likely_pathogenic	0.9496	pathogenic	-1.908	Destabilizing	1.0	D	0.788	deleterious	D	0.645327993	None	None	N
Y/I	0.8185	likely_pathogenic	0.768	pathogenic	-0.748	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.9978	pathogenic	-1.936	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/L	0.7836	likely_pathogenic	0.7686	pathogenic	-0.748	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
Y/M	0.952	likely_pathogenic	0.9397	pathogenic	-0.833	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9729	likely_pathogenic	0.9725	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.645529798	None	None	N
Y/P	0.9969	likely_pathogenic	0.9974	pathogenic	-1.264	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/Q	0.9968	likely_pathogenic	0.9966	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9902	likely_pathogenic	0.9901	pathogenic	-2.179	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/S	0.9699	likely_pathogenic	0.9712	pathogenic	-3.226	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.645529798	None	None	N
Y/T	0.986	likely_pathogenic	0.9853	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/V	0.7293	likely_pathogenic	0.708	pathogenic	-1.264	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/W	0.6405	likely_pathogenic	0.6572	pathogenic	-0.114	Destabilizing	1.0	D	0.783	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.