TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6918	20977;20978;20979	chr2:178725452;178725451;178725450	chr2:179590179;179590178;179590177
N2AB	6601	20026;20027;20028	chr2:178725452;178725451;178725450	chr2:179590179;179590178;179590177
N2A	5674	17245;17246;17247	chr2:178725452;178725451;178725450	chr2:179590179;179590178;179590177
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-53
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.5634
• 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
E/K	None	None	0.549	N	0.317	0.226	0.295623431141	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41779E-04	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
E/A	0.1653	likely_benign	0.1624	benign	-0.598	Destabilizing	0.201	N	0.289	neutral	N	0.513126989	None	None	N
E/C	0.8786	likely_pathogenic	0.8638	pathogenic	-0.232	Destabilizing	0.992	D	0.367	neutral	None	None	None	None	N
E/D	0.1379	likely_benign	0.1235	benign	-0.551	Destabilizing	0.002	N	0.164	neutral	N	0.49148228	None	None	N
E/F	0.7045	likely_pathogenic	0.6704	pathogenic	-0.23	Destabilizing	0.85	D	0.377	neutral	None	None	None	None	N
E/G	0.1506	likely_benign	0.1523	benign	-0.873	Destabilizing	0.549	D	0.334	neutral	N	0.486443706	None	None	N
E/H	0.4861	ambiguous	0.4695	ambiguous	-0.194	Destabilizing	0.972	D	0.319	neutral	None	None	None	None	N
E/I	0.3546	ambiguous	0.326	benign	0.121	Stabilizing	0.739	D	0.346	neutral	None	None	None	None	N
E/K	0.1531	likely_benign	0.1556	benign	-0.087	Destabilizing	0.549	D	0.317	neutral	N	0.500869768	None	None	N
E/L	0.3334	likely_benign	0.3134	benign	0.121	Stabilizing	0.217	N	0.374	neutral	None	None	None	None	N
E/M	0.448	ambiguous	0.4246	ambiguous	0.329	Stabilizing	0.127	N	0.354	neutral	None	None	None	None	N
E/N	0.2676	likely_benign	0.2423	benign	-0.481	Destabilizing	0.447	N	0.269	neutral	None	None	None	None	N
E/P	0.786	likely_pathogenic	0.7853	pathogenic	-0.097	Destabilizing	0.92	D	0.301	neutral	None	None	None	None	N
E/Q	0.1471	likely_benign	0.1433	benign	-0.395	Destabilizing	0.549	D	0.363	neutral	N	0.506064944	None	None	N
E/R	0.2879	likely_benign	0.2924	benign	0.203	Stabilizing	0.92	D	0.291	neutral	None	None	None	None	N
E/S	0.1957	likely_benign	0.1843	benign	-0.701	Destabilizing	0.059	N	0.191	neutral	None	None	None	None	N
E/T	0.2363	likely_benign	0.2215	benign	-0.477	Destabilizing	0.447	N	0.303	neutral	None	None	None	None	N
E/V	0.2063	likely_benign	0.1899	benign	-0.097	Destabilizing	0.379	N	0.335	neutral	N	0.490077784	None	None	N
E/W	0.9081	likely_pathogenic	0.8958	pathogenic	-0.008	Destabilizing	0.992	D	0.465	neutral	None	None	None	None	N
E/Y	0.632	likely_pathogenic	0.5983	pathogenic	0.016	Stabilizing	0.92	D	0.353	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.