TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16336	49231;49232;49233	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
N2AB	14695	44308;44309;44310	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
N2A	13768	41527;41528;41529	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
N2B	7271	22036;22037;22038	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
Novex-1	7396	22411;22412;22413	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
Novex-2	7463	22612;22613;22614	chr2:178614508;178614507;178614506	chr2:179479235;179479234;179479233
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-110
• Domain position: 75
• Structural Position: 162
• Q(SASA): 0.7141
• 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/A	None	None	0.001	N	0.103	0.09	0.239305524855	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	0	None	0	0	None	0	0	0	0	0
V/L	None	None	0.017	N	0.251	0.063	0.208000267992	gnomAD-4.0.0	1.5965E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43843E-05	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
V/A	0.1682	likely_benign	0.1343	benign	-0.311	Destabilizing	0.001	N	0.103	neutral	N	0.461274251	None	None	I
V/C	0.6547	likely_pathogenic	0.6433	pathogenic	-0.749	Destabilizing	0.836	D	0.286	neutral	None	None	None	None	I
V/D	0.4296	ambiguous	0.3183	benign	-0.38	Destabilizing	0.418	N	0.33	neutral	None	None	None	None	I
V/E	0.4044	ambiguous	0.3099	benign	-0.503	Destabilizing	0.351	N	0.303	neutral	N	0.440480396	None	None	I
V/F	0.2687	likely_benign	0.2519	benign	-0.737	Destabilizing	0.716	D	0.313	neutral	None	None	None	None	I
V/G	0.2149	likely_benign	0.1876	benign	-0.363	Destabilizing	0.101	N	0.315	neutral	N	0.474184059	None	None	I
V/H	0.5623	ambiguous	0.5074	ambiguous	-0.014	Destabilizing	0.94	D	0.276	neutral	None	None	None	None	I
V/I	0.0803	likely_benign	0.084	benign	-0.319	Destabilizing	0.002	N	0.167	neutral	None	None	None	None	I
V/K	0.3668	ambiguous	0.2603	benign	-0.355	Destabilizing	0.418	N	0.305	neutral	None	None	None	None	I
V/L	0.2597	likely_benign	0.2332	benign	-0.319	Destabilizing	0.017	N	0.251	neutral	N	0.489479334	None	None	I
V/M	0.1988	likely_benign	0.1957	benign	-0.522	Destabilizing	0.655	D	0.221	neutral	N	0.49465076	None	None	I
V/N	0.2322	likely_benign	0.1935	benign	-0.137	Destabilizing	0.418	N	0.303	neutral	None	None	None	None	I
V/P	0.4029	ambiguous	0.307	benign	-0.289	Destabilizing	0.593	D	0.322	neutral	None	None	None	None	I
V/Q	0.3557	ambiguous	0.2994	benign	-0.362	Destabilizing	0.716	D	0.327	neutral	None	None	None	None	I
V/R	0.3716	ambiguous	0.2635	benign	0.093	Stabilizing	0.418	N	0.288	neutral	None	None	None	None	I
V/S	0.1609	likely_benign	0.1356	benign	-0.429	Destabilizing	0.001	N	0.114	neutral	None	None	None	None	I
V/T	0.1512	likely_benign	0.1317	benign	-0.462	Destabilizing	None	N	0.092	neutral	None	None	None	None	I
V/W	0.8935	likely_pathogenic	0.8925	pathogenic	-0.797	Destabilizing	0.983	D	0.271	neutral	None	None	None	None	I
V/Y	0.6176	likely_pathogenic	0.5717	pathogenic	-0.515	Destabilizing	0.836	D	0.288	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.