TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5741	17446;17447;17448	chr2:178731545;178731544;178731543	chr2:179596272;179596271;179596270
N2AB	5424	16495;16496;16497	chr2:178731545;178731544;178731543	chr2:179596272;179596271;179596270
N2A	4497	13714;13715;13716	chr2:178731545;178731544;178731543	chr2:179596272;179596271;179596270
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-41
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2594
• 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
S/C	rs794729614	None	0.996	N	0.57	0.275	0.5073929853	gnomAD-4.0.0	2.05619E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7021E-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
S/A	0.0815	likely_benign	0.0841	benign	-0.959	Destabilizing	0.061	N	0.135	neutral	N	0.418307099	None	None	N
S/C	0.1034	likely_benign	0.0999	benign	-0.67	Destabilizing	0.996	D	0.57	neutral	N	0.495135874	None	None	N
S/D	0.7787	likely_pathogenic	0.8017	pathogenic	-0.141	Destabilizing	0.969	D	0.527	neutral	None	None	None	None	N
S/E	0.7857	likely_pathogenic	0.797	pathogenic	-0.151	Destabilizing	0.969	D	0.481	neutral	None	None	None	None	N
S/F	0.2649	likely_benign	0.292	benign	-1.277	Destabilizing	0.976	D	0.611	neutral	N	0.495135874	None	None	N
S/G	0.1743	likely_benign	0.1957	benign	-1.167	Destabilizing	0.863	D	0.419	neutral	None	None	None	None	N
S/H	0.5667	likely_pathogenic	0.5975	pathogenic	-1.639	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
S/I	0.1562	likely_benign	0.168	benign	-0.508	Destabilizing	0.759	D	0.495	neutral	None	None	None	None	N
S/K	0.9012	likely_pathogenic	0.9206	pathogenic	-0.554	Destabilizing	0.969	D	0.481	neutral	None	None	None	None	N
S/L	0.1219	likely_benign	0.1413	benign	-0.508	Destabilizing	0.02	N	0.323	neutral	None	None	None	None	N
S/M	0.2509	likely_benign	0.2758	benign	-0.154	Destabilizing	0.982	D	0.61	neutral	None	None	None	None	N
S/N	0.3407	ambiguous	0.3916	ambiguous	-0.466	Destabilizing	0.99	D	0.533	neutral	None	None	None	None	N
S/P	0.8163	likely_pathogenic	0.835	pathogenic	-0.629	Destabilizing	0.988	D	0.626	neutral	D	0.525285423	None	None	N
S/Q	0.7181	likely_pathogenic	0.7432	pathogenic	-0.704	Destabilizing	0.997	D	0.567	neutral	None	None	None	None	N
S/R	0.823	likely_pathogenic	0.8574	pathogenic	-0.469	Destabilizing	0.991	D	0.619	neutral	None	None	None	None	N
S/T	0.0947	likely_benign	0.0996	benign	-0.585	Destabilizing	0.826	D	0.433	neutral	N	0.41013312	None	None	N
S/V	0.1433	likely_benign	0.1523	benign	-0.629	Destabilizing	0.079	N	0.311	neutral	None	None	None	None	N
S/W	0.5421	ambiguous	0.5816	pathogenic	-1.164	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
S/Y	0.2552	likely_benign	0.2842	benign	-0.91	Destabilizing	0.996	D	0.61	neutral	D	0.524938706	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.