TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32005	96238;96239;96240	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
N2AB	30364	91315;91316;91317	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
N2A	29437	88534;88535;88536	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
N2B	22940	69043;69044;69045	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
Novex-1	23065	69418;69419;69420	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
Novex-2	23132	69619;69620;69621	chr2:178544216;178544215;178544214	chr2:179408943;179408942;179408941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-121
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0824
• 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
P/S	None	None	0.995	N	0.789	0.422	0.437100570223	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1593	likely_benign	0.1522	benign	-2.243	Highly Destabilizing	0.603	D	0.465	neutral	N	0.503700771	None	None	N
P/C	0.7849	likely_pathogenic	0.7867	pathogenic	-2.294	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/D	0.991	likely_pathogenic	0.9871	pathogenic	-3.37	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
P/E	0.9692	likely_pathogenic	0.9589	pathogenic	-3.203	Highly Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
P/F	0.9839	likely_pathogenic	0.9797	pathogenic	-1.33	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/G	0.8334	likely_pathogenic	0.8053	pathogenic	-2.692	Highly Destabilizing	0.993	D	0.764	deleterious	None	None	None	None	N
P/H	0.9685	likely_pathogenic	0.9585	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.82	deleterious	N	0.506996134	None	None	N
P/I	0.7232	likely_pathogenic	0.7037	pathogenic	-0.999	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
P/K	0.9819	likely_pathogenic	0.9764	pathogenic	-1.914	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
P/L	0.5225	ambiguous	0.4714	ambiguous	-0.999	Destabilizing	0.997	D	0.78	deleterious	D	0.5309951	None	None	N
P/M	0.7849	likely_pathogenic	0.7647	pathogenic	-1.322	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/N	0.9574	likely_pathogenic	0.9479	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/Q	0.9307	likely_pathogenic	0.9157	pathogenic	-2.229	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/R	0.954	likely_pathogenic	0.9436	pathogenic	-1.585	Destabilizing	0.999	D	0.814	deleterious	N	0.506235666	None	None	N
P/S	0.6696	likely_pathogenic	0.6296	pathogenic	-2.784	Highly Destabilizing	0.995	D	0.789	deleterious	N	0.505221708	None	None	N
P/T	0.4534	ambiguous	0.4183	ambiguous	-2.494	Highly Destabilizing	0.997	D	0.764	deleterious	N	0.503700771	None	None	N
P/V	0.4705	ambiguous	0.4501	ambiguous	-1.389	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
P/W	0.9959	likely_pathogenic	0.9938	pathogenic	-1.759	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
P/Y	0.9875	likely_pathogenic	0.9824	pathogenic	-1.479	Destabilizing	1.0	D	0.835	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.