TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5505	16738;16739;16740	chr2:178732548;178732547;178732546	chr2:179597275;179597274;179597273
N2AB	5188	15787;15788;15789	chr2:178732548;178732547;178732546	chr2:179597275;179597274;179597273
N2A	4261	13006;13007;13008	chr2:178732548;178732547;178732546	chr2:179597275;179597274;179597273
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-38
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1067
• 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/N	rs2080739721	None	0.999	N	0.645	0.304	0.156986980423	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	None	0	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
S/A	0.1071	likely_benign	0.1035	benign	-0.965	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	N
S/C	0.1428	likely_benign	0.1411	benign	-0.588	Destabilizing	1.0	D	0.828	deleterious	N	0.47393023	None	None	N
S/D	0.902	likely_pathogenic	0.9294	pathogenic	-1.562	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/E	0.9515	likely_pathogenic	0.9649	pathogenic	-1.334	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
S/F	0.5756	likely_pathogenic	0.6227	pathogenic	-0.684	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
S/G	0.1572	likely_benign	0.1737	benign	-1.37	Destabilizing	0.999	D	0.646	neutral	N	0.454189676	None	None	N
S/H	0.8276	likely_pathogenic	0.8542	pathogenic	-1.536	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/I	0.4011	ambiguous	0.4481	ambiguous	0.084	Stabilizing	1.0	D	0.857	deleterious	N	0.503039629	None	None	N
S/K	0.9896	likely_pathogenic	0.9927	pathogenic	-0.078	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
S/L	0.2993	likely_benign	0.3216	benign	0.084	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
S/M	0.441	ambiguous	0.4652	ambiguous	-0.08	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/N	0.4716	ambiguous	0.5539	ambiguous	-0.863	Destabilizing	0.999	D	0.645	neutral	N	0.48747553	None	None	N
S/P	0.8678	likely_pathogenic	0.8873	pathogenic	-0.234	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/Q	0.93	likely_pathogenic	0.9439	pathogenic	-0.562	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
S/R	0.9802	likely_pathogenic	0.9856	pathogenic	-0.522	Destabilizing	1.0	D	0.849	deleterious	N	0.489302327	None	None	N
S/T	0.1292	likely_benign	0.1298	benign	-0.518	Destabilizing	0.999	D	0.611	neutral	N	0.416247363	None	None	N
S/V	0.3331	likely_benign	0.3498	ambiguous	-0.234	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
S/W	0.7669	likely_pathogenic	0.8063	pathogenic	-0.958	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/Y	0.5043	ambiguous	0.5411	ambiguous	-0.509	Destabilizing	1.0	D	0.859	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.