TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8203	24832;24833;24834	chr2:178718499;178718498;178718497	chr2:179583226;179583225;179583224
N2AB	7886	23881;23882;23883	chr2:178718499;178718498;178718497	chr2:179583226;179583225;179583224
N2A	6959	21100;21101;21102	chr2:178718499;178718498;178718497	chr2:179583226;179583225;179583224
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-67
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3213
• 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/N	None	None	None	N	0.153	0.15	0.176091768786	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/R	None	None	0.175	N	0.505	0.285	0.308278614506	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	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
S/A	0.0946	likely_benign	0.0848	benign	-0.556	Destabilizing	0.025	N	0.355	neutral	None	None	None	None	N
S/C	0.1413	likely_benign	0.1184	benign	-0.351	Destabilizing	0.001	N	0.343	neutral	N	0.504729453	None	None	N
S/D	0.2869	likely_benign	0.2735	benign	-0.061	Destabilizing	0.055	N	0.385	neutral	None	None	None	None	N
S/E	0.305	likely_benign	0.2997	benign	-0.015	Destabilizing	0.104	N	0.382	neutral	None	None	None	None	N
S/F	0.1756	likely_benign	0.1559	benign	-0.542	Destabilizing	0.124	N	0.527	neutral	None	None	None	None	N
S/G	0.1256	likely_benign	0.1096	benign	-0.859	Destabilizing	0.042	N	0.362	neutral	N	0.492359189	None	None	N
S/H	0.1825	likely_benign	0.189	benign	-1.233	Destabilizing	0.667	D	0.475	neutral	None	None	None	None	N
S/I	0.1393	likely_benign	0.1286	benign	0.151	Stabilizing	None	N	0.331	neutral	N	0.4831163	None	None	N
S/K	0.3078	likely_benign	0.3071	benign	-0.514	Destabilizing	0.104	N	0.381	neutral	None	None	None	None	N
S/L	0.1099	likely_benign	0.0999	benign	0.151	Stabilizing	0.009	N	0.382	neutral	None	None	None	None	N
S/M	0.171	likely_benign	0.1638	benign	0.181	Stabilizing	0.497	N	0.478	neutral	None	None	None	None	N
S/N	0.0956	likely_benign	0.0949	benign	-0.574	Destabilizing	None	N	0.153	neutral	N	0.498584398	None	None	N
S/P	0.8482	likely_pathogenic	0.7817	pathogenic	-0.049	Destabilizing	0.364	N	0.529	neutral	None	None	None	None	N
S/Q	0.2696	likely_benign	0.2787	benign	-0.582	Destabilizing	0.364	N	0.466	neutral	None	None	None	None	N
S/R	0.2368	likely_benign	0.2384	benign	-0.538	Destabilizing	0.175	N	0.505	neutral	N	0.487193968	None	None	N
S/T	0.063	likely_benign	0.0619	benign	-0.536	Destabilizing	None	N	0.141	neutral	N	0.38281602	None	None	N
S/V	0.1619	likely_benign	0.146	benign	-0.049	Destabilizing	None	N	0.325	neutral	None	None	None	None	N
S/W	0.2818	likely_benign	0.2676	benign	-0.598	Destabilizing	0.958	D	0.539	neutral	None	None	None	None	N
S/Y	0.1351	likely_benign	0.1269	benign	-0.286	Destabilizing	0.004	N	0.335	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.