TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1769	5530;5531;5532	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
N2AB	1769	5530;5531;5532	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
N2A	1769	5530;5531;5532	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
N2B	1723	5392;5393;5394	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
Novex-1	1723	5392;5393;5394	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
Novex-2	1723	5392;5393;5394	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284
Novex-3	1769	5530;5531;5532	chr2:178776559;178776558;178776557	chr2:179641286;179641285;179641284

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-8
• Domain position: 67
• Structural Position: 146
• Q(SASA): 0.3914
• 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/P	None	None	0.002	N	0.137	0.316	0.0920862733494	gnomAD-4.0.0	1.59371E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85659E-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	0.0714	likely_benign	0.0659	benign	-0.581	Destabilizing	0.007	N	0.077	neutral	N	0.445446608	None	None	I
S/C	0.2319	likely_benign	0.2199	benign	-0.442	Destabilizing	0.99	D	0.287	neutral	N	0.521682791	None	None	I
S/D	0.7206	likely_pathogenic	0.7053	pathogenic	0.139	Stabilizing	0.447	N	0.209	neutral	None	None	None	None	I
S/E	0.6961	likely_pathogenic	0.6652	pathogenic	0.07	Stabilizing	0.617	D	0.192	neutral	None	None	None	None	I
S/F	0.4597	ambiguous	0.4401	ambiguous	-1.028	Destabilizing	0.963	D	0.359	neutral	N	0.510488151	None	None	I
S/G	0.153	likely_benign	0.1413	benign	-0.737	Destabilizing	0.25	N	0.255	neutral	None	None	None	None	I
S/H	0.5256	ambiguous	0.5005	ambiguous	-1.192	Destabilizing	0.85	D	0.285	neutral	None	None	None	None	I
S/I	0.3484	ambiguous	0.3487	ambiguous	-0.292	Destabilizing	0.92	D	0.379	neutral	None	None	None	None	I
S/K	0.873	likely_pathogenic	0.8515	pathogenic	-0.601	Destabilizing	0.447	N	0.207	neutral	None	None	None	None	I
S/L	0.1762	likely_benign	0.1738	benign	-0.292	Destabilizing	0.617	D	0.339	neutral	None	None	None	None	I
S/M	0.3416	ambiguous	0.3422	ambiguous	-0.041	Destabilizing	0.972	D	0.291	neutral	None	None	None	None	I
S/N	0.2783	likely_benign	0.2683	benign	-0.384	Destabilizing	0.005	N	0.225	neutral	None	None	None	None	I
S/P	0.0857	likely_benign	0.0814	benign	-0.358	Destabilizing	0.002	N	0.137	neutral	N	0.326908303	None	None	I
S/Q	0.5421	ambiguous	0.5106	ambiguous	-0.616	Destabilizing	0.85	D	0.293	neutral	None	None	None	None	I
S/R	0.8243	likely_pathogenic	0.7906	pathogenic	-0.39	Destabilizing	0.85	D	0.313	neutral	None	None	None	None	I
S/T	0.1241	likely_benign	0.1204	benign	-0.502	Destabilizing	0.334	N	0.271	neutral	N	0.50296553	None	None	I
S/V	0.2745	likely_benign	0.2668	benign	-0.358	Destabilizing	0.617	D	0.323	neutral	None	None	None	None	I
S/W	0.6586	likely_pathogenic	0.6447	pathogenic	-0.983	Destabilizing	0.992	D	0.479	neutral	None	None	None	None	I
S/Y	0.4314	ambiguous	0.4164	ambiguous	-0.729	Destabilizing	0.963	D	0.357	neutral	D	0.571250551	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.