TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1142	3649;3650;3651	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
N2AB	1142	3649;3650;3651	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
N2A	1142	3649;3650;3651	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
N2B	1096	3511;3512;3513	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
Novex-1	1096	3511;3512;3513	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
Novex-2	1096	3511;3512;3513	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945
Novex-3	1142	3649;3650;3651	chr2:178781220;178781219;178781218	chr2:179645947;179645946;179645945

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-4
• Domain position: 61
• Structural Position: 139
• Q(SASA): 0.2119
• 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
V/L	None	None	0.625	N	0.527	0.34	0.598413393357	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.2723	likely_benign	0.2354	benign	-1.599	Destabilizing	0.625	D	0.408	neutral	N	0.507091466	None	None	N
V/C	0.8785	likely_pathogenic	0.8299	pathogenic	-1.333	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
V/D	0.5341	ambiguous	0.4655	ambiguous	-1.253	Destabilizing	0.525	D	0.529	neutral	None	None	None	None	N
V/E	0.2243	likely_benign	0.1932	benign	-1.153	Destabilizing	0.002	N	0.448	neutral	N	0.453418675	None	None	N
V/F	0.2743	likely_benign	0.2405	benign	-0.967	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	N
V/G	0.4401	ambiguous	0.3793	ambiguous	-2.02	Highly Destabilizing	0.801	D	0.581	neutral	D	0.570632147	None	None	N
V/H	0.6496	likely_pathogenic	0.5912	pathogenic	-1.582	Destabilizing	0.974	D	0.634	neutral	None	None	None	None	N
V/I	0.0895	likely_benign	0.088	benign	-0.502	Destabilizing	0.817	D	0.537	neutral	None	None	None	None	N
V/K	0.5348	ambiguous	0.4892	ambiguous	-1.313	Destabilizing	0.525	D	0.537	neutral	None	None	None	None	N
V/L	0.2122	likely_benign	0.1952	benign	-0.502	Destabilizing	0.625	D	0.527	neutral	N	0.440044455	None	None	N
V/M	0.1569	likely_benign	0.1361	benign	-0.581	Destabilizing	0.989	D	0.559	neutral	N	0.496319001	None	None	N
V/N	0.4126	ambiguous	0.3534	ambiguous	-1.297	Destabilizing	0.842	D	0.584	neutral	None	None	None	None	N
V/P	0.9925	likely_pathogenic	0.992	pathogenic	-0.834	Destabilizing	0.915	D	0.591	neutral	None	None	None	None	N
V/Q	0.3475	ambiguous	0.3063	benign	-1.295	Destabilizing	0.728	D	0.569	neutral	None	None	None	None	N
V/R	0.5307	ambiguous	0.494	ambiguous	-1.02	Destabilizing	0.842	D	0.591	neutral	None	None	None	None	N
V/S	0.3105	likely_benign	0.2642	benign	-1.979	Destabilizing	0.842	D	0.563	neutral	None	None	None	None	N
V/T	0.233	likely_benign	0.1971	benign	-1.746	Destabilizing	0.688	D	0.536	neutral	None	None	None	None	N
V/W	0.91	likely_pathogenic	0.8903	pathogenic	-1.248	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
V/Y	0.7007	likely_pathogenic	0.6689	pathogenic	-0.91	Destabilizing	0.991	D	0.574	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.