TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23409	70450;70451;70452	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
N2AB	21768	65527;65528;65529	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
N2A	20841	62746;62747;62748	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
N2B	14344	43255;43256;43257	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
Novex-1	14469	43630;43631;43632	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
Novex-2	14536	43831;43832;43833	chr2:178575907;178575906;178575905	chr2:179440634;179440633;179440632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-129
• Domain position: 65
• Structural Position: 149
• Q(SASA): 0.166
• 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
D/G	rs1709909119	None	0.958	D	0.759	0.865	0.628213846089	gnomAD-4.0.0	1.7107E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24894E-05	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
D/A	0.9907	likely_pathogenic	0.9962	pathogenic	0.383	Stabilizing	0.988	D	0.816	deleterious	D	0.625067153	None	None	N
D/C	0.9948	likely_pathogenic	0.9976	pathogenic	0.344	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
D/E	0.9569	likely_pathogenic	0.9766	pathogenic	-0.696	Destabilizing	0.067	N	0.368	neutral	D	0.591585441	None	None	N
D/F	0.9963	likely_pathogenic	0.9985	pathogenic	0.97	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
D/G	0.9905	likely_pathogenic	0.9959	pathogenic	-0.1	Destabilizing	0.958	D	0.759	deleterious	D	0.625268957	None	None	N
D/H	0.9732	likely_pathogenic	0.9849	pathogenic	0.531	Stabilizing	0.998	D	0.818	deleterious	D	0.550713744	None	None	N
D/I	0.9967	likely_pathogenic	0.9989	pathogenic	1.684	Stabilizing	0.995	D	0.87	deleterious	None	None	None	None	N
D/K	0.9964	likely_pathogenic	0.9985	pathogenic	0.164	Stabilizing	0.982	D	0.792	deleterious	None	None	None	None	N
D/L	0.9934	likely_pathogenic	0.9971	pathogenic	1.684	Stabilizing	0.991	D	0.877	deleterious	None	None	None	None	N
D/M	0.9979	likely_pathogenic	0.9993	pathogenic	2.139	Highly Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/N	0.9316	likely_pathogenic	0.9704	pathogenic	-0.697	Destabilizing	0.988	D	0.777	deleterious	D	0.623452719	None	None	N
D/P	0.9996	likely_pathogenic	0.9998	pathogenic	1.281	Stabilizing	0.995	D	0.824	deleterious	None	None	None	None	N
D/Q	0.9921	likely_pathogenic	0.9968	pathogenic	-0.312	Destabilizing	0.982	D	0.789	deleterious	None	None	None	None	N
D/R	0.9958	likely_pathogenic	0.9982	pathogenic	0.089	Stabilizing	0.991	D	0.862	deleterious	None	None	None	None	N
D/S	0.9643	likely_pathogenic	0.9869	pathogenic	-0.969	Destabilizing	0.968	D	0.697	prob.neutral	None	None	None	None	N
D/T	0.9944	likely_pathogenic	0.9982	pathogenic	-0.52	Destabilizing	0.991	D	0.816	deleterious	None	None	None	None	N
D/V	0.9907	likely_pathogenic	0.9967	pathogenic	1.281	Stabilizing	0.994	D	0.875	deleterious	D	0.625672566	None	None	N
D/W	0.9992	likely_pathogenic	0.9996	pathogenic	0.954	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/Y	0.9738	likely_pathogenic	0.9883	pathogenic	1.224	Stabilizing	0.999	D	0.878	deleterious	D	0.625470762	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.