TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23616	71071;71072;71073	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
N2AB	21975	66148;66149;66150	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
N2A	21048	63367;63368;63369	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
N2B	14551	43876;43877;43878	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
Novex-1	14676	44251;44252;44253	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
Novex-2	14743	44452;44453;44454	chr2:178575286;178575285;178575284	chr2:179440013;179440012;179440011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-59
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.3226
• 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
P/H	None	None	1.0	D	0.771	0.457	0.633664262589	gnomAD-4.0.0	1.59222E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8594E-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
P/A	0.0985	likely_benign	0.1076	benign	-1.452	Destabilizing	1.0	D	0.721	prob.delet.	N	0.489571491	None	None	I
P/C	0.6801	likely_pathogenic	0.7071	pathogenic	-0.714	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/D	0.8712	likely_pathogenic	0.8877	pathogenic	-1.602	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/E	0.6847	likely_pathogenic	0.7038	pathogenic	-1.649	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/F	0.6989	likely_pathogenic	0.7058	pathogenic	-1.252	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/G	0.4812	ambiguous	0.5271	ambiguous	-1.713	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
P/H	0.4686	ambiguous	0.4874	ambiguous	-1.319	Destabilizing	1.0	D	0.771	deleterious	D	0.52237664	None	None	I
P/I	0.6075	likely_pathogenic	0.5997	pathogenic	-0.842	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
P/K	0.587	likely_pathogenic	0.6075	pathogenic	-1.338	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
P/L	0.3251	likely_benign	0.3282	benign	-0.842	Destabilizing	1.0	D	0.773	deleterious	N	0.519841745	None	None	I
P/M	0.6089	likely_pathogenic	0.6213	pathogenic	-0.486	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/N	0.7382	likely_pathogenic	0.7623	pathogenic	-0.969	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/Q	0.3998	ambiguous	0.4102	ambiguous	-1.223	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
P/R	0.392	ambiguous	0.4055	ambiguous	-0.688	Destabilizing	1.0	D	0.78	deleterious	D	0.526135622	None	None	I
P/S	0.2421	likely_benign	0.2653	benign	-1.338	Destabilizing	1.0	D	0.771	deleterious	N	0.507524388	None	None	I
P/T	0.2817	likely_benign	0.2993	benign	-1.301	Destabilizing	1.0	D	0.764	deleterious	D	0.526389112	None	None	I
P/V	0.4017	ambiguous	0.4004	ambiguous	-1.012	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
P/W	0.8368	likely_pathogenic	0.8431	pathogenic	-1.42	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
P/Y	0.726	likely_pathogenic	0.7344	pathogenic	-1.187	Destabilizing	1.0	D	0.797	deleterious	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.