TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35656	107191;107192;107193	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
N2AB	34015	102268;102269;102270	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
N2A	33088	99487;99488;99489	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
N2B	26591	79996;79997;79998	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
Novex-1	26716	80371;80372;80373	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
Novex-2	26783	80572;80573;80574	chr2:178528785;178528784;178528783	chr2:179393512;179393511;179393510
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-167
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.5535
• 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/L	None	None	1.0	N	0.621	0.466	0.70075097299	gnomAD-4.0.0	1.5942E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8659E-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	0.1074	likely_benign	0.1027	benign	-0.338	Destabilizing	0.997	D	0.422	neutral	N	0.483708159	None	None	N
S/C	0.2942	likely_benign	0.2926	benign	-0.233	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
S/D	0.5522	ambiguous	0.5235	ambiguous	0.162	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
S/E	0.6582	likely_pathogenic	0.6234	pathogenic	0.047	Stabilizing	0.999	D	0.536	neutral	None	None	None	None	N
S/F	0.2835	likely_benign	0.2642	benign	-1.089	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
S/G	0.1821	likely_benign	0.1678	benign	-0.376	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
S/H	0.5499	ambiguous	0.509	ambiguous	-0.855	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
S/I	0.2881	likely_benign	0.2636	benign	-0.365	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
S/K	0.8007	likely_pathogenic	0.761	pathogenic	-0.275	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
S/L	0.1462	likely_benign	0.1389	benign	-0.365	Destabilizing	1.0	D	0.621	neutral	N	0.484401593	None	None	N
S/M	0.3419	ambiguous	0.3083	benign	-0.076	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
S/N	0.259	likely_benign	0.2294	benign	0.005	Stabilizing	0.999	D	0.507	neutral	None	None	None	None	N
S/P	0.5701	likely_pathogenic	0.5536	ambiguous	-0.333	Destabilizing	1.0	D	0.648	neutral	N	0.484574951	None	None	N
S/Q	0.6845	likely_pathogenic	0.6392	pathogenic	-0.275	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
S/R	0.7205	likely_pathogenic	0.6809	pathogenic	-0.085	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
S/T	0.1071	likely_benign	0.0997	benign	-0.141	Destabilizing	0.999	D	0.448	neutral	N	0.482668009	None	None	N
S/V	0.3045	likely_benign	0.2759	benign	-0.333	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
S/W	0.4873	ambiguous	0.463	ambiguous	-1.109	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
S/Y	0.3003	likely_benign	0.2778	benign	-0.815	Destabilizing	1.0	D	0.697	prob.neutral	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.