TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16431	49516;49517;49518	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
N2AB	14790	44593;44594;44595	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
N2A	13863	41812;41813;41814	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
N2B	7366	22321;22322;22323	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
Novex-1	7491	22696;22697;22698	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
Novex-2	7558	22897;22898;22899	chr2:178614106;178614105;178614104	chr2:179478833;179478832;179478831
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: Fn3-6
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.5989
• Predicted PPI site: I

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	N	0.689	0.348	0.417334834585	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/H	None	None	0.998	N	0.463	0.376	0.342865806769	gnomAD-4.0.0	1.36942E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.1599E-05	1.65904E-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	0.9577	likely_pathogenic	0.9423	pathogenic	-0.541	Destabilizing	0.985	D	0.637	neutral	None	None	None	None	I
Y/C	0.6823	likely_pathogenic	0.593	pathogenic	0.208	Stabilizing	1.0	D	0.689	prob.neutral	N	0.465795238	None	None	I
Y/D	0.9704	likely_pathogenic	0.953	pathogenic	0.929	Stabilizing	0.998	D	0.68	prob.neutral	N	0.507369343	None	None	I
Y/E	0.9885	likely_pathogenic	0.9833	pathogenic	0.903	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	I
Y/F	0.0975	likely_benign	0.0963	benign	-0.298	Destabilizing	0.031	N	0.224	neutral	N	0.460274118	None	None	I
Y/G	0.9701	likely_pathogenic	0.9532	pathogenic	-0.719	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
Y/H	0.7501	likely_pathogenic	0.6614	pathogenic	0.27	Stabilizing	0.998	D	0.463	neutral	N	0.469286234	None	None	I
Y/I	0.7521	likely_pathogenic	0.7526	pathogenic	-0.102	Destabilizing	0.97	D	0.58	neutral	None	None	None	None	I
Y/K	0.9862	likely_pathogenic	0.98	pathogenic	0.325	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	I
Y/L	0.8	likely_pathogenic	0.7549	pathogenic	-0.102	Destabilizing	0.871	D	0.57	neutral	None	None	None	None	I
Y/M	0.8951	likely_pathogenic	0.8687	pathogenic	0.011	Stabilizing	0.999	D	0.572	neutral	None	None	None	None	I
Y/N	0.8372	likely_pathogenic	0.7668	pathogenic	0.159	Stabilizing	0.998	D	0.668	neutral	N	0.463916374	None	None	I
Y/P	0.9954	likely_pathogenic	0.9933	pathogenic	-0.228	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
Y/Q	0.973	likely_pathogenic	0.9619	pathogenic	0.195	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	I
Y/R	0.9624	likely_pathogenic	0.9455	pathogenic	0.553	Stabilizing	0.999	D	0.67	neutral	None	None	None	None	I
Y/S	0.9168	likely_pathogenic	0.8817	pathogenic	-0.255	Destabilizing	0.998	D	0.603	neutral	N	0.468553738	None	None	I
Y/T	0.9594	likely_pathogenic	0.9453	pathogenic	-0.188	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	I
Y/V	0.7146	likely_pathogenic	0.6906	pathogenic	-0.228	Destabilizing	0.97	D	0.594	neutral	None	None	None	None	I
Y/W	0.662	likely_pathogenic	0.6075	pathogenic	-0.46	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	I

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.