TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8781	26566;26567;26568	chr2:178714433;178714432;178714431	chr2:179579160;179579159;179579158
N2AB	8464	25615;25616;25617	chr2:178714433;178714432;178714431	chr2:179579160;179579159;179579158
N2A	7537	22834;22835;22836	chr2:178714433;178714432;178714431	chr2:179579160;179579159;179579158
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-73
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.6046
• 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
D/A	rs2077152071	None	0.328	N	0.369	0.238	0.250039746154	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78011E-04
D/A	rs2077152071	None	0.328	N	0.369	0.238	0.250039746154	gnomAD-4.0.0	6.57168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78011E-04
D/N	None	None	0.604	N	0.343	0.328	0.143124449307	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
D/A	0.1272	likely_benign	0.1398	benign	0.09	Stabilizing	0.328	N	0.369	neutral	N	0.454793515	None	None	N
D/C	0.5657	likely_pathogenic	0.6125	pathogenic	0.01	Stabilizing	0.968	D	0.571	neutral	None	None	None	None	N
D/E	0.0963	likely_benign	0.0973	benign	-0.373	Destabilizing	None	N	0.243	neutral	N	0.43198482	None	None	N
D/F	0.5321	ambiguous	0.5953	pathogenic	-0.135	Destabilizing	0.971	D	0.522	neutral	None	None	None	None	N
D/G	0.1066	likely_benign	0.1163	benign	0.02	Stabilizing	0.413	N	0.321	neutral	N	0.494590717	None	None	N
D/H	0.21	likely_benign	0.231	benign	0.396	Stabilizing	0.972	D	0.371	neutral	N	0.475811059	None	None	N
D/I	0.3228	likely_benign	0.3792	ambiguous	0.2	Stabilizing	0.248	N	0.414	neutral	None	None	None	None	N
D/K	0.1821	likely_benign	0.1924	benign	0.477	Stabilizing	0.89	D	0.333	neutral	None	None	None	None	N
D/L	0.3142	likely_benign	0.3523	ambiguous	0.2	Stabilizing	0.699	D	0.433	neutral	None	None	None	None	N
D/M	0.5127	ambiguous	0.5674	pathogenic	0.09	Stabilizing	0.979	D	0.517	neutral	None	None	None	None	N
D/N	0.083	likely_benign	0.0927	benign	0.366	Stabilizing	0.604	D	0.343	neutral	N	0.46614982	None	None	N
D/P	0.3786	ambiguous	0.3579	ambiguous	0.18	Stabilizing	0.394	N	0.363	neutral	None	None	None	None	N
D/Q	0.2016	likely_benign	0.2177	benign	0.341	Stabilizing	0.752	D	0.361	neutral	None	None	None	None	N
D/R	0.2158	likely_benign	0.2397	benign	0.572	Stabilizing	0.942	D	0.435	neutral	None	None	None	None	N
D/S	0.0958	likely_benign	0.1067	benign	0.274	Stabilizing	0.393	N	0.321	neutral	None	None	None	None	N
D/T	0.199	likely_benign	0.2195	benign	0.334	Stabilizing	0.669	D	0.321	neutral	None	None	None	None	N
D/V	0.1989	likely_benign	0.2253	benign	0.18	Stabilizing	0.234	N	0.44	neutral	N	0.458213783	None	None	N
D/W	0.7629	likely_pathogenic	0.8012	pathogenic	-0.156	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
D/Y	0.2188	likely_benign	0.2602	benign	0.071	Stabilizing	0.987	D	0.52	neutral	N	0.455896378	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.