TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21099	63520;63521;63522	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
N2AB	19458	58597;58598;58599	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
N2A	18531	55816;55817;55818	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
N2B	12034	36325;36326;36327	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
Novex-1	12159	36700;36701;36702	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
Novex-2	12226	36901;36902;36903	chr2:178588112;178588111;178588110	chr2:179452839;179452838;179452837
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-41
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0886
• 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	rs1180774898	-1.472	1.0	D	0.864	0.862	0.854735952166	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	8.91E-06	0
Y/C	rs1180774898	-1.472	1.0	D	0.864	0.862	0.854735952166	gnomAD-4.0.0	3.18631E-06	None	None	None	None	N	None	0	0	None	0	2.78443E-05	None	0	0	0	0	3.02755E-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
Y/A	0.9945	likely_pathogenic	0.9945	pathogenic	-3.507	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/C	0.8996	likely_pathogenic	0.9054	pathogenic	-1.845	Destabilizing	1.0	D	0.864	deleterious	D	0.645320864	None	None	N
Y/D	0.989	likely_pathogenic	0.989	pathogenic	-3.926	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.645522669	None	None	N
Y/E	0.9979	likely_pathogenic	0.9978	pathogenic	-3.706	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/F	0.2383	likely_benign	0.2508	benign	-1.56	Destabilizing	0.999	D	0.649	neutral	N	0.521952016	None	None	N
Y/G	0.9872	likely_pathogenic	0.9857	pathogenic	-3.911	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/H	0.9665	likely_pathogenic	0.9644	pathogenic	-2.675	Highly Destabilizing	1.0	D	0.775	deleterious	D	0.629099699	None	None	N
Y/I	0.9648	likely_pathogenic	0.9674	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9981	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.9449	likely_pathogenic	0.9394	pathogenic	-2.129	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
Y/M	0.9753	likely_pathogenic	0.9748	pathogenic	-1.743	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/N	0.956	likely_pathogenic	0.9521	pathogenic	-3.475	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.645522669	None	None	N
Y/P	0.9986	likely_pathogenic	0.9986	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9974	pathogenic	-3.186	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/R	0.9947	likely_pathogenic	0.9943	pathogenic	-2.43	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/S	0.977	likely_pathogenic	0.9762	pathogenic	-3.734	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.645522669	None	None	N
Y/T	0.9921	likely_pathogenic	0.9919	pathogenic	-3.396	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.9456	likely_pathogenic	0.9502	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/W	0.7524	likely_pathogenic	0.7611	pathogenic	-0.819	Destabilizing	1.0	D	0.766	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.