TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7608	23047;23048;23049	chr2:178721197;178721196;178721195	chr2:179585924;179585923;179585922
N2AB	7291	22096;22097;22098	chr2:178721197;178721196;178721195	chr2:179585924;179585923;179585922
N2A	6364	19315;19316;19317	chr2:178721197;178721196;178721195	chr2:179585924;179585923;179585922
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-61
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1936
• 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	1.0	D	0.871	0.704	0.695117004628	gnomAD-4.0.0	1.64723E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.93949E-05	0	0	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	0.7538	likely_pathogenic	0.7392	pathogenic	-1.668	Destabilizing	0.999	D	0.815	deleterious	D	0.609351396	None	None	N
P/C	0.9897	likely_pathogenic	0.9856	pathogenic	-1.316	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/D	0.9995	likely_pathogenic	0.9994	pathogenic	-1.414	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
P/E	0.9978	likely_pathogenic	0.9968	pathogenic	-1.394	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/F	0.9989	likely_pathogenic	0.9987	pathogenic	-1.305	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/G	0.9888	likely_pathogenic	0.9866	pathogenic	-2.009	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/H	0.9973	likely_pathogenic	0.9962	pathogenic	-1.489	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/I	0.9621	likely_pathogenic	0.9623	pathogenic	-0.821	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9976	pathogenic	-1.269	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/L	0.9023	likely_pathogenic	0.8944	pathogenic	-0.821	Destabilizing	1.0	D	0.867	deleterious	D	0.60952284	None	None	N
P/M	0.9869	likely_pathogenic	0.9857	pathogenic	-0.727	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/N	0.9989	likely_pathogenic	0.9986	pathogenic	-1.115	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/Q	0.9935	likely_pathogenic	0.9919	pathogenic	-1.278	Destabilizing	1.0	D	0.859	deleterious	D	0.651514281	None	None	N
P/R	0.9937	likely_pathogenic	0.9914	pathogenic	-0.795	Destabilizing	1.0	D	0.871	deleterious	D	0.651514281	None	None	N
P/S	0.9743	likely_pathogenic	0.9712	pathogenic	-1.722	Destabilizing	1.0	D	0.871	deleterious	D	0.651110673	None	None	N
P/T	0.9608	likely_pathogenic	0.9542	pathogenic	-1.585	Destabilizing	1.0	D	0.867	deleterious	D	0.651312477	None	None	N
P/V	0.8936	likely_pathogenic	0.8967	pathogenic	-1.07	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9995	pathogenic	-1.466	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9991	pathogenic	-1.171	Destabilizing	1.0	D	0.872	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.