TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9070	27433;27434;27435	chr2:178712817;178712816;178712815	chr2:179577544;179577543;179577542
N2AB	8753	26482;26483;26484	chr2:178712817;178712816;178712815	chr2:179577544;179577543;179577542
N2A	7826	23701;23702;23703	chr2:178712817;178712816;178712815	chr2:179577544;179577543;179577542
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-76
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4443
• 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/D	rs1226337905	None	None	N	0.093	0.099	0.143124449307	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1226337905	None	None	N	0.093	0.099	0.143124449307	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-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
E/A	0.1405	likely_benign	0.1355	benign	-0.16	Destabilizing	None	N	0.094	neutral	N	0.491279098	None	None	N
E/C	0.7366	likely_pathogenic	0.7556	pathogenic	-0.05	Destabilizing	0.356	N	0.283	neutral	None	None	None	None	N
E/D	0.1265	likely_benign	0.1245	benign	-0.236	Destabilizing	None	N	0.093	neutral	N	0.478937058	None	None	N
E/F	0.5828	likely_pathogenic	0.6027	pathogenic	-0.1	Destabilizing	0.356	N	0.343	neutral	None	None	None	None	N
E/G	0.1225	likely_benign	0.1234	benign	-0.313	Destabilizing	0.012	N	0.24	neutral	D	0.533464976	None	None	N
E/H	0.2868	likely_benign	0.2748	benign	0.329	Stabilizing	0.214	N	0.214	neutral	None	None	None	None	N
E/I	0.2959	likely_benign	0.308	benign	0.194	Stabilizing	0.038	N	0.365	neutral	None	None	None	None	N
E/K	0.0872	likely_benign	0.0873	benign	0.5	Stabilizing	None	N	0.099	neutral	N	0.486863108	None	None	N
E/L	0.2839	likely_benign	0.2864	benign	0.194	Stabilizing	0.016	N	0.256	neutral	None	None	None	None	N
E/M	0.3502	ambiguous	0.3717	ambiguous	0.117	Stabilizing	0.356	N	0.294	neutral	None	None	None	None	N
E/N	0.2138	likely_benign	0.205	benign	0.172	Stabilizing	0.038	N	0.143	neutral	None	None	None	None	N
E/P	0.6858	likely_pathogenic	0.685	pathogenic	0.096	Stabilizing	0.136	N	0.309	neutral	None	None	None	None	N
E/Q	0.0984	likely_benign	0.092	benign	0.203	Stabilizing	None	N	0.093	neutral	N	0.521285112	None	None	N
E/R	0.1394	likely_benign	0.1391	benign	0.694	Stabilizing	0.016	N	0.148	neutral	None	None	None	None	N
E/S	0.1606	likely_benign	0.1545	benign	0.042	Stabilizing	0.016	N	0.154	neutral	None	None	None	None	N
E/T	0.1724	likely_benign	0.1738	benign	0.175	Stabilizing	None	N	0.09	neutral	None	None	None	None	N
E/V	0.1795	likely_benign	0.1829	benign	0.096	Stabilizing	None	N	0.161	neutral	N	0.521458471	None	None	N
E/W	0.6952	likely_pathogenic	0.7225	pathogenic	0.004	Stabilizing	0.864	D	0.289	neutral	None	None	None	None	N
E/Y	0.4492	ambiguous	0.4569	ambiguous	0.139	Stabilizing	0.356	N	0.346	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.