TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17695	53308;53309;53310	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
N2AB	16054	48385;48386;48387	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
N2A	15127	45604;45605;45606	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
N2B	8630	26113;26114;26115	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
Novex-1	8755	26488;26489;26490	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
Novex-2	8822	26689;26690;26691	chr2:178607605;178607604;178607603	chr2:179472332;179472331;179472330
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-113
• Domain position: 19
• Structural Position: 34
• Q(SASA): 0.6263
• 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
V/G	rs2055207996	None	0.024	N	0.499	0.088	0.489938136499	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/G	rs2055207996	None	0.024	N	0.499	0.088	0.489938136499	gnomAD-4.0.0	6.5786E-06	None	None	None	None	I	None	2.41278E-05	0	None	0	0	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
V/A	0.1527	likely_benign	0.1427	benign	-0.478	Destabilizing	0.005	N	0.189	neutral	N	0.468063916	None	None	I
V/C	0.6386	likely_pathogenic	0.6269	pathogenic	-0.581	Destabilizing	0.628	D	0.488	neutral	None	None	None	None	I
V/D	0.3	likely_benign	0.3082	benign	-0.288	Destabilizing	0.016	N	0.514	neutral	None	None	None	None	I
V/E	0.2297	likely_benign	0.2382	benign	-0.411	Destabilizing	None	N	0.235	neutral	N	0.472045584	None	None	I
V/F	0.1367	likely_benign	0.1268	benign	-0.752	Destabilizing	0.072	N	0.554	neutral	None	None	None	None	I
V/G	0.2653	likely_benign	0.2449	benign	-0.602	Destabilizing	0.024	N	0.499	neutral	N	0.505910228	None	None	I
V/H	0.3791	ambiguous	0.3836	ambiguous	-0.204	Destabilizing	None	N	0.351	neutral	None	None	None	None	I
V/I	0.0723	likely_benign	0.0688	benign	-0.305	Destabilizing	None	N	0.136	neutral	None	None	None	None	I
V/K	0.2411	likely_benign	0.2339	benign	-0.397	Destabilizing	None	N	0.23	neutral	None	None	None	None	I
V/L	0.1611	likely_benign	0.1507	benign	-0.305	Destabilizing	0.002	N	0.205	neutral	N	0.507526381	None	None	I
V/M	0.1123	likely_benign	0.1058	benign	-0.275	Destabilizing	0.171	N	0.36	neutral	N	0.519724888	None	None	I
V/N	0.1975	likely_benign	0.1989	benign	-0.135	Destabilizing	0.072	N	0.538	neutral	None	None	None	None	I
V/P	0.8944	likely_pathogenic	0.881	pathogenic	-0.328	Destabilizing	0.136	N	0.592	neutral	None	None	None	None	I
V/Q	0.2488	likely_benign	0.2508	benign	-0.401	Destabilizing	0.038	N	0.567	neutral	None	None	None	None	I
V/R	0.2192	likely_benign	0.218	benign	0.131	Stabilizing	None	N	0.331	neutral	None	None	None	None	I
V/S	0.1694	likely_benign	0.1628	benign	-0.491	Destabilizing	0.016	N	0.417	neutral	None	None	None	None	I
V/T	0.1059	likely_benign	0.1049	benign	-0.515	Destabilizing	None	N	0.136	neutral	None	None	None	None	I
V/W	0.7002	likely_pathogenic	0.6769	pathogenic	-0.825	Destabilizing	0.864	D	0.566	neutral	None	None	None	None	I
V/Y	0.395	ambiguous	0.3914	ambiguous	-0.517	Destabilizing	0.072	N	0.551	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.