TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32339	97240;97241;97242	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
N2AB	30698	92317;92318;92319	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
N2A	29771	89536;89537;89538	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
N2B	23274	70045;70046;70047	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
Novex-1	23399	70420;70421;70422	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
Novex-2	23466	70621;70622;70623	chr2:178542839;178542838;178542837	chr2:179407566;179407565;179407564
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-154
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.1919
• 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/P	None	None	0.999	N	0.744	0.671	0.47290127212	gnomAD-4.0.0	2.73676E-06	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	2.69836E-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	0.0926	likely_benign	0.0891	benign	-0.576	Destabilizing	0.973	D	0.444	neutral	D	0.533715692	None	None	N
S/C	0.1208	likely_benign	0.1187	benign	-0.257	Destabilizing	1.0	D	0.735	prob.delet.	N	0.500944018	None	None	N
S/D	0.5708	likely_pathogenic	0.5369	ambiguous	-0.386	Destabilizing	0.996	D	0.559	neutral	None	None	None	None	N
S/E	0.5915	likely_pathogenic	0.5665	pathogenic	-0.258	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
S/F	0.2421	likely_benign	0.204	benign	-0.621	Destabilizing	0.999	D	0.789	deleterious	D	0.522616051	None	None	N
S/G	0.125	likely_benign	0.1283	benign	-0.92	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
S/H	0.3439	ambiguous	0.338	benign	-1.155	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
S/I	0.1832	likely_benign	0.1706	benign	0.267	Stabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
S/K	0.7341	likely_pathogenic	0.7118	pathogenic	-0.115	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
S/L	0.1248	likely_benign	0.1126	benign	0.267	Stabilizing	0.992	D	0.643	neutral	None	None	None	None	N
S/M	0.2015	likely_benign	0.1984	benign	0.192	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/N	0.1528	likely_benign	0.1701	benign	-0.553	Destabilizing	0.996	D	0.549	neutral	None	None	None	None	N
S/P	0.9131	likely_pathogenic	0.8993	pathogenic	0.021	Stabilizing	0.999	D	0.744	deleterious	N	0.511793344	None	None	N
S/Q	0.4663	ambiguous	0.4676	ambiguous	-0.408	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
S/R	0.6452	likely_pathogenic	0.6139	pathogenic	-0.292	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
S/T	0.0776	likely_benign	0.0753	benign	-0.406	Destabilizing	0.543	D	0.399	neutral	N	0.461738164	None	None	N
S/V	0.1641	likely_benign	0.1471	benign	0.021	Stabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
S/W	0.457	ambiguous	0.4044	ambiguous	-0.793	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/Y	0.2431	likely_benign	0.2279	benign	-0.364	Destabilizing	0.999	D	0.787	deleterious	N	0.500797984	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.