TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23983	72172;72173;72174	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
N2AB	22342	67249;67250;67251	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
N2A	21415	64468;64469;64470	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
N2B	14918	44977;44978;44979	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
Novex-1	15043	45352;45353;45354	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
Novex-2	15110	45553;45554;45555	chr2:178574185;178574184;178574183	chr2:179438912;179438911;179438910
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-62
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4219
• 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/G	rs1299777918	None	0.642	N	0.505	0.211	0.318828661733	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
E/G	rs1299777918	None	0.642	N	0.505	0.211	0.318828661733	gnomAD-4.0.0	6.40763E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19693E-05	0	0
E/K	None	None	0.27	N	0.367	0.24	0.201204373187	gnomAD-4.0.0	1.36864E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79913E-06	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	0.1494	likely_benign	0.1733	benign	-0.712	Destabilizing	0.425	N	0.423	neutral	N	0.461414798	None	None	N
E/C	0.7437	likely_pathogenic	0.7724	pathogenic	-0.437	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	N
E/D	0.2062	likely_benign	0.2207	benign	-1.059	Destabilizing	0.27	N	0.377	neutral	N	0.507976594	None	None	N
E/F	0.6695	likely_pathogenic	0.7093	pathogenic	0.127	Stabilizing	0.893	D	0.6	neutral	None	None	None	None	N
E/G	0.2365	likely_benign	0.2716	benign	-1.12	Destabilizing	0.642	D	0.505	neutral	N	0.509515389	None	None	N
E/H	0.3782	ambiguous	0.3955	ambiguous	-0.052	Destabilizing	0.944	D	0.501	neutral	None	None	None	None	N
E/I	0.2594	likely_benign	0.2821	benign	0.416	Stabilizing	0.031	N	0.514	neutral	None	None	None	None	N
E/K	0.1667	likely_benign	0.1699	benign	-0.559	Destabilizing	0.27	N	0.367	neutral	N	0.485465093	None	None	N
E/L	0.4112	ambiguous	0.4459	ambiguous	0.416	Stabilizing	0.329	N	0.479	neutral	None	None	None	None	N
E/M	0.3711	ambiguous	0.4116	ambiguous	0.781	Stabilizing	0.176	N	0.454	neutral	None	None	None	None	N
E/N	0.2443	likely_benign	0.2745	benign	-1.172	Destabilizing	0.031	N	0.369	neutral	None	None	None	None	N
E/P	0.955	likely_pathogenic	0.9625	pathogenic	0.062	Stabilizing	0.944	D	0.585	neutral	None	None	None	None	N
E/Q	0.1227	likely_benign	0.1263	benign	-0.984	Destabilizing	0.023	N	0.329	neutral	N	0.438519295	None	None	N
E/R	0.2724	likely_benign	0.2796	benign	-0.192	Destabilizing	0.543	D	0.424	neutral	None	None	None	None	N
E/S	0.1678	likely_benign	0.1868	benign	-1.514	Destabilizing	0.329	N	0.381	neutral	None	None	None	None	N
E/T	0.1508	likely_benign	0.1685	benign	-1.165	Destabilizing	0.031	N	0.334	neutral	None	None	None	None	N
E/V	0.1689	likely_benign	0.1901	benign	0.062	Stabilizing	0.27	N	0.462	neutral	N	0.516961436	None	None	N
E/W	0.892	likely_pathogenic	0.911	pathogenic	0.419	Stabilizing	0.995	D	0.604	neutral	None	None	None	None	N
E/Y	0.5146	ambiguous	0.5546	ambiguous	0.403	Stabilizing	0.981	D	0.601	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.