TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33612	101059;101060;101061	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
N2AB	31971	96136;96137;96138	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
N2A	31044	93355;93356;93357	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
N2B	24547	73864;73865;73866	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
Novex-1	24672	74239;74240;74241	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
Novex-2	24739	74440;74441;74442	chr2:178535781;178535780;178535779	chr2:179400508;179400507;179400506
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-159
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3153
• 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/G	None	None	0.545	N	0.391	0.136	0.388334884743	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	0.3699	ambiguous	0.1866	benign	-0.818	Destabilizing	0.001	N	0.108	neutral	N	0.448703711	None	None	N
V/C	0.9103	likely_pathogenic	0.8072	pathogenic	-0.821	Destabilizing	0.962	D	0.385	neutral	None	None	None	None	N
V/D	0.6799	likely_pathogenic	0.3849	ambiguous	-0.378	Destabilizing	0.54	D	0.415	neutral	None	None	None	None	N
V/E	0.5984	likely_pathogenic	0.33	benign	-0.444	Destabilizing	0.222	N	0.357	neutral	N	0.427808364	None	None	N
V/F	0.4443	ambiguous	0.2388	benign	-0.731	Destabilizing	0.861	D	0.405	neutral	None	None	None	None	N
V/G	0.4997	ambiguous	0.2794	benign	-1.032	Destabilizing	0.545	D	0.391	neutral	N	0.486491308	None	None	N
V/H	0.8395	likely_pathogenic	0.6202	pathogenic	-0.465	Destabilizing	0.009	N	0.353	neutral	None	None	None	None	N
V/I	0.1047	likely_benign	0.0856	benign	-0.38	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
V/K	0.7019	likely_pathogenic	0.3951	ambiguous	-0.715	Destabilizing	0.293	N	0.355	neutral	None	None	None	None	N
V/L	0.4911	ambiguous	0.2907	benign	-0.38	Destabilizing	0.023	N	0.301	neutral	N	0.486491308	None	None	N
V/M	0.284	likely_benign	0.1669	benign	-0.437	Destabilizing	0.77	D	0.371	neutral	N	0.505597144	None	None	N
V/N	0.4482	ambiguous	0.2294	benign	-0.514	Destabilizing	0.002	N	0.32	neutral	None	None	None	None	N
V/P	0.7377	likely_pathogenic	0.5195	ambiguous	-0.489	Destabilizing	0.466	N	0.405	neutral	None	None	None	None	N
V/Q	0.6226	likely_pathogenic	0.3824	ambiguous	-0.712	Destabilizing	0.673	D	0.406	neutral	None	None	None	None	N
V/R	0.6566	likely_pathogenic	0.3704	ambiguous	-0.183	Destabilizing	0.005	N	0.336	neutral	None	None	None	None	N
V/S	0.4593	ambiguous	0.2272	benign	-0.984	Destabilizing	0.323	N	0.347	neutral	None	None	None	None	N
V/T	0.3067	likely_benign	0.1647	benign	-0.938	Destabilizing	0.277	N	0.187	neutral	None	None	None	None	N
V/W	0.9561	likely_pathogenic	0.8722	pathogenic	-0.821	Destabilizing	0.997	D	0.485	neutral	None	None	None	None	N
V/Y	0.8342	likely_pathogenic	0.6379	pathogenic	-0.536	Destabilizing	0.861	D	0.412	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.