TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26159	78700;78701;78702	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
N2AB	24518	73777;73778;73779	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
N2A	23591	70996;70997;70998	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
N2B	17094	51505;51506;51507	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
Novex-1	17219	51880;51881;51882	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
Novex-2	17286	52081;52082;52083	chr2:178567657;178567656;178567655	chr2:179432384;179432383;179432382
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: Fn3-78
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1125
• 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/N	None	None	1.0	D	0.873	0.907	0.947038774563	gnomAD-4.0.0	2.05456E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70046E-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	0.9943	likely_pathogenic	0.9942	pathogenic	-3.157	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/C	0.876	likely_pathogenic	0.8663	pathogenic	-1.573	Destabilizing	1.0	D	0.873	deleterious	D	0.671078577	None	None	N
Y/D	0.9951	likely_pathogenic	0.9951	pathogenic	-3.553	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.680365163	None	None	N
Y/E	0.9979	likely_pathogenic	0.9979	pathogenic	-3.327	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/F	0.3343	likely_benign	0.3083	benign	-1.169	Destabilizing	0.999	D	0.738	prob.delet.	D	0.646510203	None	None	N
Y/G	0.9822	likely_pathogenic	0.9831	pathogenic	-3.577	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/H	0.9618	likely_pathogenic	0.9603	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.680365163	None	None	N
Y/I	0.9763	likely_pathogenic	0.9756	pathogenic	-1.744	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/K	0.9976	likely_pathogenic	0.9976	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.9526	likely_pathogenic	0.9533	pathogenic	-1.744	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
Y/M	0.9796	likely_pathogenic	0.9782	pathogenic	-1.465	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/N	0.9664	likely_pathogenic	0.9647	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.696414885	None	None	N
Y/P	0.9992	likely_pathogenic	0.9992	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9963	likely_pathogenic	0.9961	pathogenic	-2.67	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/R	0.992	likely_pathogenic	0.992	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/S	0.9783	likely_pathogenic	0.9788	pathogenic	-3.257	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.696616689	None	None	N
Y/T	0.9922	likely_pathogenic	0.9922	pathogenic	-2.907	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9469	likely_pathogenic	0.9466	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/W	0.8344	likely_pathogenic	0.8188	pathogenic	-0.42	Destabilizing	1.0	D	0.825	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.