TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35311	106156;106157;106158	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
N2AB	33670	101233;101234;101235	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
N2A	32743	98452;98453;98454	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
N2B	26246	78961;78962;78963	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
Novex-1	26371	79336;79337;79338	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
Novex-2	26438	79537;79538;79539	chr2:178530684;178530683;178530682	chr2:179395411;179395410;179395409
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-165
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.1365
• 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/I	None	None	None	N	0.184	0.074	0.0920862733494	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-05

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	0.095	likely_benign	0.1295	benign	-0.621	Destabilizing	None	N	0.138	neutral	N	0.387086744	None	None	N
V/C	0.584	likely_pathogenic	0.6582	pathogenic	-0.609	Destabilizing	0.326	N	0.464	neutral	None	None	None	None	N
V/D	0.1593	likely_benign	0.2232	benign	-0.246	Destabilizing	0.193	N	0.538	neutral	None	None	None	None	N
V/E	0.1741	likely_benign	0.2365	benign	-0.343	Destabilizing	0.049	N	0.467	neutral	N	0.429434799	None	None	N
V/F	0.0996	likely_benign	0.1199	benign	-0.712	Destabilizing	0.193	N	0.506	neutral	None	None	None	None	N
V/G	0.1238	likely_benign	0.1701	benign	-0.793	Destabilizing	0.025	N	0.487	neutral	N	0.41067568	None	None	N
V/H	0.3661	ambiguous	0.4702	ambiguous	-0.404	Destabilizing	0.848	D	0.521	neutral	None	None	None	None	N
V/I	0.0712	likely_benign	0.0759	benign	-0.306	Destabilizing	None	N	0.184	neutral	N	0.439958437	None	None	N
V/K	0.2644	likely_benign	0.3428	ambiguous	-0.553	Destabilizing	0.064	N	0.47	neutral	None	None	None	None	N
V/L	0.1106	likely_benign	0.1429	benign	-0.306	Destabilizing	None	N	0.169	neutral	N	0.457677406	None	None	N
V/M	0.1049	likely_benign	0.123	benign	-0.319	Destabilizing	0.193	N	0.472	neutral	None	None	None	None	N
V/N	0.1376	likely_benign	0.1882	benign	-0.247	Destabilizing	0.326	N	0.553	neutral	None	None	None	None	N
V/P	0.2311	likely_benign	0.3376	benign	-0.375	Destabilizing	0.193	N	0.515	neutral	None	None	None	None	N
V/Q	0.2231	likely_benign	0.2908	benign	-0.472	Destabilizing	0.326	N	0.516	neutral	None	None	None	None	N
V/R	0.2266	likely_benign	0.2872	benign	-0.066	Destabilizing	0.193	N	0.547	neutral	None	None	None	None	N
V/S	0.106	likely_benign	0.1425	benign	-0.656	Destabilizing	0.033	N	0.437	neutral	None	None	None	None	N
V/T	0.1229	likely_benign	0.1619	benign	-0.649	Destabilizing	0.033	N	0.406	neutral	None	None	None	None	N
V/W	0.648	likely_pathogenic	0.7324	pathogenic	-0.806	Destabilizing	0.848	D	0.545	neutral	None	None	None	None	N
V/Y	0.3635	ambiguous	0.4358	ambiguous	-0.513	Destabilizing	0.326	N	0.492	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.