TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2566	7921;7922;7923	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
N2AB	2566	7921;7922;7923	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
N2A	2566	7921;7922;7923	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
N2B	2520	7783;7784;7785	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
Novex-1	2520	7783;7784;7785	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
Novex-2	2520	7783;7784;7785	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993
Novex-3	2566	7921;7922;7923	chr2:178773268;178773267;178773266	chr2:179637995;179637994;179637993

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-15
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1669
• 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
N/D	None	None	0.425	N	0.441	0.2	0.110078149338	gnomAD-4.0.0	1.59095E-06	None	None	None	None	N	None	0	0	None	0	2.77809E-05	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
N/A	0.2452	likely_benign	0.2281	benign	-1.239	Destabilizing	0.3	N	0.461	neutral	None	None	None	None	N
N/C	0.1941	likely_benign	0.1834	benign	-0.457	Destabilizing	0.995	D	0.535	neutral	None	None	None	None	N
N/D	0.2373	likely_benign	0.21	benign	-1.667	Destabilizing	0.425	N	0.441	neutral	N	0.397018809	None	None	N
N/E	0.3808	ambiguous	0.3561	ambiguous	-1.396	Destabilizing	0.329	N	0.418	neutral	None	None	None	None	N
N/F	0.3166	likely_benign	0.2861	benign	-0.689	Destabilizing	0.893	D	0.577	neutral	None	None	None	None	N
N/G	0.3897	ambiguous	0.3657	ambiguous	-1.669	Destabilizing	0.495	N	0.424	neutral	None	None	None	None	N
N/H	0.0674	likely_benign	0.0642	benign	-1.102	Destabilizing	0.006	N	0.277	neutral	N	0.36274004	None	None	N
N/I	0.1223	likely_benign	0.1055	benign	-0.073	Destabilizing	0.473	N	0.539	neutral	N	0.41266723	None	None	N
N/K	0.204	likely_benign	0.1861	benign	-0.14	Destabilizing	0.27	N	0.435	neutral	N	0.383390913	None	None	N
N/L	0.1516	likely_benign	0.1399	benign	-0.073	Destabilizing	0.003	N	0.458	neutral	None	None	None	None	N
N/M	0.2254	likely_benign	0.2003	benign	0.096	Stabilizing	0.893	D	0.505	neutral	None	None	None	None	N
N/P	0.953	likely_pathogenic	0.9505	pathogenic	-0.435	Destabilizing	0.828	D	0.515	neutral	None	None	None	None	N
N/Q	0.2558	likely_benign	0.2413	benign	-0.705	Destabilizing	0.031	N	0.242	neutral	None	None	None	None	N
N/R	0.2136	likely_benign	0.2113	benign	-0.439	Destabilizing	0.543	D	0.459	neutral	None	None	None	None	N
N/S	0.1103	likely_benign	0.103	benign	-1.241	Destabilizing	0.27	N	0.388	neutral	N	0.38365418	None	None	N
N/T	0.1202	likely_benign	0.1086	benign	-0.766	Destabilizing	0.003	N	0.187	neutral	N	0.285074559	None	None	N
N/V	0.1568	likely_benign	0.1354	benign	-0.435	Destabilizing	0.329	N	0.492	neutral	None	None	None	None	N
N/W	0.6309	likely_pathogenic	0.5985	pathogenic	-0.562	Destabilizing	0.995	D	0.546	neutral	None	None	None	None	N
N/Y	0.0794	likely_benign	0.073	benign	-0.215	Destabilizing	0.642	D	0.53	neutral	N	0.296202145	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.