TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4020	12283;12284;12285	chr2:178741175;178741174;178741173	chr2:179605902;179605901;179605900
N2AB	3703	11332;11333;11334	chr2:178741175;178741174;178741173	chr2:179605902;179605901;179605900
N2A	None	None	chr2:None	chr2:None
N2B	3657	11194;11195;11196	chr2:178741175;178741174;178741173	chr2:179605902;179605901;179605900
Novex-1	3782	11569;11570;11571	chr2:178741175;178741174;178741173	chr2:179605902;179605901;179605900
Novex-2	3849	11770;11771;11772	chr2:178741175;178741174;178741173	chr2:179605902;179605901;179605900
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-28
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1323
• Predicted PPI site: I

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/Y	rs1273620132	-0.361	0.56	D	0.598	0.292	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
S/Y	rs1273620132	-0.361	0.56	D	0.598	0.292	None	gnomAD-4.0.0	2.73764E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69831E-06	0	1.65667E-05

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	0.0785	likely_benign	0.0835	benign	-0.744	Destabilizing	None	N	0.092	neutral	N	0.412188418	None	None	I
S/C	0.1294	likely_benign	0.1192	benign	-0.492	Destabilizing	None	N	0.431	neutral	D	0.577622495	None	None	I
S/D	0.3461	ambiguous	0.3116	benign	-0.24	Destabilizing	0.072	N	0.421	neutral	None	None	None	None	I
S/E	0.535	ambiguous	0.5234	ambiguous	-0.207	Destabilizing	0.072	N	0.394	neutral	None	None	None	None	I
S/F	0.3407	ambiguous	0.3532	ambiguous	-0.736	Destabilizing	0.171	N	0.615	neutral	D	0.577770987	None	None	I
S/G	0.1571	likely_benign	0.1327	benign	-1.038	Destabilizing	0.016	N	0.398	neutral	None	None	None	None	I
S/H	0.4846	ambiguous	0.4573	ambiguous	-1.43	Destabilizing	0.628	D	0.542	neutral	None	None	None	None	I
S/I	0.2432	likely_benign	0.2599	benign	-0.059	Destabilizing	0.016	N	0.53	neutral	None	None	None	None	I
S/K	0.7446	likely_pathogenic	0.7181	pathogenic	-0.685	Destabilizing	0.072	N	0.393	neutral	None	None	None	None	I
S/L	0.1761	likely_benign	0.2003	benign	-0.059	Destabilizing	0.016	N	0.541	neutral	None	None	None	None	I
S/M	0.2845	likely_benign	0.2992	benign	0.093	Stabilizing	0.356	N	0.554	neutral	None	None	None	None	I
S/N	0.1907	likely_benign	0.1744	benign	-0.701	Destabilizing	0.072	N	0.441	neutral	None	None	None	None	I
S/P	0.9347	likely_pathogenic	0.8929	pathogenic	-0.252	Destabilizing	0.106	N	0.564	neutral	D	0.577622495	None	None	I
S/Q	0.6088	likely_pathogenic	0.5844	pathogenic	-0.769	Destabilizing	0.356	N	0.512	neutral	None	None	None	None	I
S/R	0.6568	likely_pathogenic	0.6246	pathogenic	-0.654	Destabilizing	0.072	N	0.563	neutral	None	None	None	None	I
S/T	0.0987	likely_benign	0.1044	benign	-0.692	Destabilizing	None	N	0.137	neutral	N	0.485524716	None	None	I
S/V	0.2186	likely_benign	0.2439	benign	-0.252	Destabilizing	None	N	0.37	neutral	None	None	None	None	I
S/W	0.5629	ambiguous	0.5317	ambiguous	-0.736	Destabilizing	0.864	D	0.604	neutral	None	None	None	None	I
S/Y	0.2548	likely_benign	0.2517	benign	-0.462	Destabilizing	0.56	D	0.598	neutral	D	0.601225419	None	None	I

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.