TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17703	53332;53333;53334	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
N2AB	16062	48409;48410;48411	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
N2A	15135	45628;45629;45630	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
N2B	8638	26137;26138;26139	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
Novex-1	8763	26512;26513;26514	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
Novex-2	8830	26713;26714;26715	chr2:178607581;178607580;178607579	chr2:179472308;179472307;179472306
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-113
• Domain position: 27
• Structural Position: 45
• Q(SASA): 0.4589
• 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
T/A	None	None	0.011	D	0.149	0.198	0.229924730088	gnomAD-4.0.0	1.59233E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88338E-05	0	0	0	0
T/S	None	None	0.123	N	0.148	0.091	0.204665344411	gnomAD-4.0.0	1.59233E-06	None	None	None	None	I	None	0	0	None	0	2.77423E-05	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
T/A	0.0783	likely_benign	0.0765	benign	-0.401	Destabilizing	0.011	N	0.149	neutral	D	0.523034552	None	None	I
T/C	0.4549	ambiguous	0.4538	ambiguous	-0.262	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	I
T/D	0.2664	likely_benign	0.2493	benign	0.074	Stabilizing	0.919	D	0.385	neutral	None	None	None	None	I
T/E	0.1511	likely_benign	0.1445	benign	0.017	Stabilizing	0.919	D	0.365	neutral	None	None	None	None	I
T/F	0.2975	likely_benign	0.2903	benign	-0.778	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	I
T/G	0.2352	likely_benign	0.2332	benign	-0.57	Destabilizing	0.702	D	0.415	neutral	None	None	None	None	I
T/H	0.2496	likely_benign	0.2403	benign	-0.85	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
T/I	0.164	likely_benign	0.1563	benign	-0.069	Destabilizing	0.968	D	0.397	neutral	N	0.486239442	None	None	I
T/K	0.1382	likely_benign	0.1376	benign	-0.471	Destabilizing	0.896	D	0.391	neutral	N	0.48033978	None	None	I
T/L	0.1091	likely_benign	0.1069	benign	-0.069	Destabilizing	0.919	D	0.34	neutral	None	None	None	None	I
T/M	0.1072	likely_benign	0.1067	benign	0.061	Stabilizing	0.999	D	0.461	neutral	None	None	None	None	I
T/N	0.1172	likely_benign	0.1185	benign	-0.26	Destabilizing	0.919	D	0.339	neutral	None	None	None	None	I
T/P	0.2967	likely_benign	0.3435	ambiguous	-0.15	Destabilizing	0.984	D	0.403	neutral	N	0.518840328	None	None	I
T/Q	0.1442	likely_benign	0.1431	benign	-0.456	Destabilizing	0.988	D	0.444	neutral	None	None	None	None	I
T/R	0.1388	likely_benign	0.1409	benign	-0.196	Destabilizing	0.984	D	0.411	neutral	D	0.524920063	None	None	I
T/S	0.1067	likely_benign	0.0997	benign	-0.465	Destabilizing	0.123	N	0.148	neutral	N	0.503368568	None	None	I
T/V	0.1187	likely_benign	0.1104	benign	-0.15	Destabilizing	0.851	D	0.289	neutral	None	None	None	None	I
T/W	0.6231	likely_pathogenic	0.6228	pathogenic	-0.789	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
T/Y	0.3	likely_benign	0.3097	benign	-0.516	Destabilizing	0.996	D	0.557	neutral	None	None	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.