TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5740	17443;17444;17445	chr2:178731548;178731547;178731546	chr2:179596275;179596274;179596273
N2AB	5423	16492;16493;16494	chr2:178731548;178731547;178731546	chr2:179596275;179596274;179596273
N2A	4496	13711;13712;13713	chr2:178731548;178731547;178731546	chr2:179596275;179596274;179596273
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-41
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5577
• 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/T	rs779492952	0.281	0.134	N	0.092	0.185	0.144782658237	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
S/T	rs779492952	0.281	0.134	N	0.092	0.185	0.144782658237	gnomAD-4.0.0	6.39799E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14952E-05	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	0.0838	likely_benign	0.0873	benign	-0.443	Destabilizing	0.079	N	0.063	neutral	None	None	None	None	I
S/C	0.1653	likely_benign	0.1589	benign	-0.244	Destabilizing	0.999	D	0.362	neutral	N	0.487809605	None	None	I
S/D	0.4414	ambiguous	0.4708	ambiguous	0.312	Stabilizing	0.759	D	0.195	neutral	None	None	None	None	I
S/E	0.5592	ambiguous	0.5591	ambiguous	0.213	Stabilizing	0.17	N	0.11	neutral	None	None	None	None	I
S/F	0.2072	likely_benign	0.2156	benign	-1.085	Destabilizing	0.997	D	0.375	neutral	None	None	None	None	I
S/G	0.121	likely_benign	0.13	benign	-0.535	Destabilizing	0.826	D	0.277	neutral	N	0.486795647	None	None	I
S/H	0.3991	ambiguous	0.4063	ambiguous	-1.067	Destabilizing	0.991	D	0.364	neutral	None	None	None	None	I
S/I	0.1777	likely_benign	0.1861	benign	-0.328	Destabilizing	0.976	D	0.385	neutral	N	0.50920125	None	None	I
S/K	0.753	likely_pathogenic	0.7639	pathogenic	-0.348	Destabilizing	0.939	D	0.193	neutral	None	None	None	None	I
S/L	0.132	likely_benign	0.1416	benign	-0.328	Destabilizing	0.939	D	0.321	neutral	None	None	None	None	I
S/M	0.2564	likely_benign	0.2639	benign	-0.01	Destabilizing	0.997	D	0.361	neutral	None	None	None	None	I
S/N	0.155	likely_benign	0.1721	benign	-0.051	Destabilizing	0.134	N	0.117	neutral	N	0.499426973	None	None	I
S/P	0.429	ambiguous	0.5227	ambiguous	-0.339	Destabilizing	0.997	D	0.373	neutral	None	None	None	None	I
S/Q	0.5579	ambiguous	0.559	ambiguous	-0.323	Destabilizing	0.939	D	0.307	neutral	None	None	None	None	I
S/R	0.6392	likely_pathogenic	0.6529	pathogenic	-0.181	Destabilizing	0.92	D	0.357	neutral	N	0.512990916	None	None	I
S/T	0.0766	likely_benign	0.0773	benign	-0.203	Destabilizing	0.134	N	0.092	neutral	N	0.42450514	None	None	I
S/V	0.1614	likely_benign	0.1634	benign	-0.339	Destabilizing	0.939	D	0.327	neutral	None	None	None	None	I
S/W	0.4017	ambiguous	0.4184	ambiguous	-1.065	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	I
S/Y	0.2147	likely_benign	0.2275	benign	-0.784	Destabilizing	0.997	D	0.373	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.