TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26914	80965;80966;80967	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
N2AB	25273	76042;76043;76044	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
N2A	24346	73261;73262;73263	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
N2B	17849	53770;53771;53772	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
Novex-1	17974	54145;54146;54147	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
Novex-2	18041	54346;54347;54348	chr2:178565392;178565391;178565390	chr2:179430119;179430118;179430117
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-139
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1719
• 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/F	None	None	0.772	N	0.577	0.215	0.432826170204	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	0	None	0	0	None	0	0	0	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	0.1054	likely_benign	0.1065	benign	-1.618	Destabilizing	0.08	N	0.37	neutral	N	0.429637948	None	None	N
V/C	0.4592	ambiguous	0.448	ambiguous	-1.369	Destabilizing	0.965	D	0.535	neutral	None	None	None	None	N
V/D	0.1791	likely_benign	0.183	benign	-1.231	Destabilizing	0.326	N	0.563	neutral	N	0.442009813	None	None	N
V/E	0.1172	likely_benign	0.1165	benign	-1.146	Destabilizing	0.002	N	0.317	neutral	None	None	None	None	N
V/F	0.0965	likely_benign	0.0922	benign	-1.129	Destabilizing	0.772	D	0.577	neutral	N	0.389172618	None	None	N
V/G	0.1274	likely_benign	0.1278	benign	-2.019	Highly Destabilizing	0.491	N	0.559	neutral	N	0.457901985	None	None	N
V/H	0.2357	likely_benign	0.2329	benign	-1.601	Destabilizing	0.901	D	0.599	neutral	None	None	None	None	N
V/I	0.0692	likely_benign	0.0675	benign	-0.58	Destabilizing	0.003	N	0.21	neutral	N	0.41349506	None	None	N
V/K	0.13	likely_benign	0.138	benign	-1.198	Destabilizing	0.001	N	0.289	neutral	None	None	None	None	N
V/L	0.0936	likely_benign	0.0922	benign	-0.58	Destabilizing	0.029	N	0.386	neutral	N	0.345152482	None	None	N
V/M	0.0735	likely_benign	0.0697	benign	-0.647	Destabilizing	0.103	N	0.403	neutral	None	None	None	None	N
V/N	0.1146	likely_benign	0.1225	benign	-1.17	Destabilizing	0.561	D	0.594	neutral	None	None	None	None	N
V/P	0.9394	likely_pathogenic	0.9301	pathogenic	-0.892	Destabilizing	0.722	D	0.589	neutral	None	None	None	None	N
V/Q	0.1135	likely_benign	0.1182	benign	-1.202	Destabilizing	0.39	N	0.555	neutral	None	None	None	None	N
V/R	0.1312	likely_benign	0.1383	benign	-0.903	Destabilizing	0.39	N	0.563	neutral	None	None	None	None	N
V/S	0.0929	likely_benign	0.0945	benign	-1.856	Destabilizing	0.209	N	0.497	neutral	None	None	None	None	N
V/T	0.091	likely_benign	0.0895	benign	-1.638	Destabilizing	0.007	N	0.205	neutral	None	None	None	None	N
V/W	0.5463	ambiguous	0.529	ambiguous	-1.381	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
V/Y	0.2869	likely_benign	0.2744	benign	-1.032	Destabilizing	0.901	D	0.581	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.