TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2893	8902;8903;8904	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
N2AB	2893	8902;8903;8904	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
N2A	2893	8902;8903;8904	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
N2B	2847	8764;8765;8766	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
Novex-1	2847	8764;8765;8766	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
Novex-2	2847	8764;8765;8766	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629
Novex-3	2893	8902;8903;8904	chr2:178769904;178769903;178769902	chr2:179634631;179634630;179634629

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-19
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1191
• 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/M	None	None	0.982	D	0.579	0.552	0.694889576946	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.5038	ambiguous	0.6362	pathogenic	-1.748	Destabilizing	0.939	D	0.452	neutral	N	0.51130012	None	None	N
V/C	0.8719	likely_pathogenic	0.9275	pathogenic	-1.274	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
V/D	0.9106	likely_pathogenic	0.9645	pathogenic	-1.962	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
V/E	0.8027	likely_pathogenic	0.9013	pathogenic	-1.933	Destabilizing	0.997	D	0.617	neutral	D	0.762976302	None	None	N
V/F	0.4274	ambiguous	0.6278	pathogenic	-1.319	Destabilizing	0.986	D	0.618	neutral	None	None	None	None	N
V/G	0.628	likely_pathogenic	0.7686	pathogenic	-2.097	Highly Destabilizing	0.997	D	0.655	neutral	D	0.688886934	None	None	N
V/H	0.9345	likely_pathogenic	0.9748	pathogenic	-1.649	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
V/I	0.0857	likely_benign	0.0909	benign	-0.862	Destabilizing	0.06	N	0.296	neutral	None	None	None	None	N
V/K	0.8248	likely_pathogenic	0.9246	pathogenic	-1.454	Destabilizing	0.993	D	0.617	neutral	None	None	None	None	N
V/L	0.3681	ambiguous	0.4627	ambiguous	-0.862	Destabilizing	0.046	N	0.263	neutral	D	0.621823121	None	None	N
V/M	0.2737	likely_benign	0.3647	ambiguous	-0.717	Destabilizing	0.982	D	0.579	neutral	D	0.761939926	None	None	N
V/N	0.814	likely_pathogenic	0.9096	pathogenic	-1.338	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
V/P	0.9869	likely_pathogenic	0.9945	pathogenic	-1.124	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
V/Q	0.7986	likely_pathogenic	0.9002	pathogenic	-1.5	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
V/R	0.8218	likely_pathogenic	0.9235	pathogenic	-0.94	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
V/S	0.7079	likely_pathogenic	0.8313	pathogenic	-1.857	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	N
V/T	0.4728	ambiguous	0.5771	pathogenic	-1.722	Destabilizing	0.953	D	0.553	neutral	None	None	None	None	N
V/W	0.971	likely_pathogenic	0.9895	pathogenic	-1.567	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
V/Y	0.8535	likely_pathogenic	0.9416	pathogenic	-1.272	Destabilizing	0.998	D	0.617	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.