TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24179	72760;72761;72762	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
N2AB	22538	67837;67838;67839	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
N2A	21611	65056;65057;65058	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
N2B	15114	45565;45566;45567	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
Novex-1	15239	45940;45941;45942	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
Novex-2	15306	46141;46142;46143	chr2:178573597;178573596;178573595	chr2:179438324;179438323;179438322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-63
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3237
• 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/I	rs1400549364	-0.338	None	N	0.117	0.057	0.12205267543	gnomAD-2.1.1	1E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.01E-05	0
V/I	rs1400549364	-0.338	None	N	0.117	0.057	0.12205267543	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1400549364	-0.338	None	N	0.117	0.057	0.12205267543	gnomAD-4.0.0	6.67919E-06	None	None	None	None	I	None	1.40252E-05	0	None	0	0	None	0	0	5.32982E-06	0	5.22612E-05

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	0.1404	likely_benign	0.1385	benign	-1.033	Destabilizing	0.001	N	0.078	neutral	N	0.407617598	None	None	I
V/C	0.6698	likely_pathogenic	0.6599	pathogenic	-0.802	Destabilizing	0.935	D	0.346	neutral	None	None	None	None	I
V/D	0.2875	likely_benign	0.28	benign	-0.95	Destabilizing	0.555	D	0.39	neutral	None	None	None	None	I
V/E	0.281	likely_benign	0.2684	benign	-0.938	Destabilizing	0.117	N	0.352	neutral	N	0.430126312	None	None	I
V/F	0.1787	likely_benign	0.1662	benign	-0.777	Destabilizing	0.235	N	0.387	neutral	None	None	None	None	I
V/G	0.1426	likely_benign	0.1378	benign	-1.297	Destabilizing	0.117	N	0.321	neutral	N	0.420645611	None	None	I
V/H	0.5753	likely_pathogenic	0.5232	ambiguous	-0.598	Destabilizing	0.935	D	0.375	neutral	None	None	None	None	I
V/I	0.0943	likely_benign	0.0935	benign	-0.411	Destabilizing	None	N	0.117	neutral	N	0.484849018	None	None	I
V/K	0.4099	ambiguous	0.3818	ambiguous	-0.864	Destabilizing	0.149	N	0.346	neutral	None	None	None	None	I
V/L	0.2054	likely_benign	0.1971	benign	-0.411	Destabilizing	None	N	0.079	neutral	N	0.465300465	None	None	I
V/M	0.1452	likely_benign	0.142	benign	-0.587	Destabilizing	0.38	N	0.375	neutral	None	None	None	None	I
V/N	0.1956	likely_benign	0.1929	benign	-0.801	Destabilizing	0.555	D	0.411	neutral	None	None	None	None	I
V/P	0.5731	likely_pathogenic	0.6093	pathogenic	-0.586	Destabilizing	0.001	N	0.263	neutral	None	None	None	None	I
V/Q	0.356	ambiguous	0.3242	benign	-0.916	Destabilizing	0.555	D	0.382	neutral	None	None	None	None	I
V/R	0.4364	ambiguous	0.4017	ambiguous	-0.394	Destabilizing	0.555	D	0.407	neutral	None	None	None	None	I
V/S	0.1609	likely_benign	0.1621	benign	-1.228	Destabilizing	0.081	N	0.291	neutral	None	None	None	None	I
V/T	0.1511	likely_benign	0.1496	benign	-1.101	Destabilizing	0.149	N	0.189	neutral	None	None	None	None	I
V/W	0.8362	likely_pathogenic	0.7886	pathogenic	-0.93	Destabilizing	0.935	D	0.473	neutral	None	None	None	None	I
V/Y	0.5201	ambiguous	0.4869	ambiguous	-0.622	Destabilizing	0.555	D	0.388	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.