TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2267	7024;7025;7026	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
N2AB	2267	7024;7025;7026	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
N2A	2267	7024;7025;7026	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
N2B	2221	6886;6887;6888	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
Novex-1	2221	6886;6887;6888	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
Novex-2	2221	6886;6887;6888	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190
Novex-3	2267	7024;7025;7026	chr2:178774465;178774464;178774463	chr2:179639192;179639191;179639190

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-12
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.753
• 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/A	None	None	0.165	N	0.371	0.271	0.519514513453	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	0.1284	likely_benign	0.1264	benign	-1.233	Destabilizing	0.165	N	0.371	neutral	N	0.497713941	None	None	N
V/C	0.6786	likely_pathogenic	0.6639	pathogenic	-0.881	Destabilizing	0.981	D	0.313	neutral	None	None	None	None	N
V/D	0.422	ambiguous	0.4182	ambiguous	-0.931	Destabilizing	0.773	D	0.377	neutral	N	0.511912347	None	None	N
V/E	0.3375	likely_benign	0.3292	benign	-0.872	Destabilizing	0.818	D	0.36	neutral	None	None	None	None	N
V/F	0.1774	likely_benign	0.1733	benign	-0.803	Destabilizing	0.627	D	0.339	neutral	N	0.510105269	None	None	N
V/G	0.2381	likely_benign	0.234	benign	-1.563	Destabilizing	0.773	D	0.364	neutral	N	0.510958047	None	None	N
V/H	0.5679	likely_pathogenic	0.5587	ambiguous	-0.913	Destabilizing	0.981	D	0.352	neutral	None	None	None	None	N
V/I	0.0716	likely_benign	0.0709	benign	-0.406	Destabilizing	0.001	N	0.185	neutral	N	0.4727538	None	None	N
V/K	0.3342	likely_benign	0.3308	benign	-0.932	Destabilizing	0.818	D	0.363	neutral	None	None	None	None	N
V/L	0.16	likely_benign	0.1535	benign	-0.406	Destabilizing	None	N	0.132	neutral	N	0.450369091	None	None	N
V/M	0.1359	likely_benign	0.131	benign	-0.561	Destabilizing	0.69	D	0.353	neutral	None	None	None	None	N
V/N	0.2959	likely_benign	0.2916	benign	-0.865	Destabilizing	0.932	D	0.363	neutral	None	None	None	None	N
V/P	0.2637	likely_benign	0.2577	benign	-0.649	Destabilizing	0.932	D	0.363	neutral	None	None	None	None	N
V/Q	0.3598	ambiguous	0.3539	ambiguous	-0.907	Destabilizing	0.932	D	0.347	neutral	None	None	None	None	N
V/R	0.3151	likely_benign	0.3068	benign	-0.584	Destabilizing	0.818	D	0.369	neutral	None	None	None	None	N
V/S	0.2098	likely_benign	0.2048	benign	-1.392	Destabilizing	0.563	D	0.371	neutral	None	None	None	None	N
V/T	0.1324	likely_benign	0.1285	benign	-1.203	Destabilizing	0.388	N	0.327	neutral	None	None	None	None	N
V/W	0.7542	likely_pathogenic	0.7354	pathogenic	-0.979	Destabilizing	0.981	D	0.403	neutral	None	None	None	None	N
V/Y	0.5195	ambiguous	0.5072	ambiguous	-0.663	Destabilizing	0.818	D	0.321	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.