TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6331	19216;19217;19218	chr2:178729047;178729046;178729045	chr2:179593774;179593773;179593772
N2AB	6014	18265;18266;18267	chr2:178729047;178729046;178729045	chr2:179593774;179593773;179593772
N2A	5087	15484;15485;15486	chr2:178729047;178729046;178729045	chr2:179593774;179593773;179593772
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-47
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.5895
• 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
I/L	rs1198892837	-0.125	0.906	N	0.297	0.128	0.505885190548	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9E-06	0
I/L	rs1198892837	-0.125	0.906	N	0.297	0.128	0.505885190548	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs1198892837	-0.125	0.906	N	0.297	0.128	0.505885190548	gnomAD-4.0.0	3.72031E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.23934E-06	0	1.60251E-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
I/A	0.2336	likely_benign	0.1984	benign	-0.729	Destabilizing	0.927	D	0.387	neutral	None	None	None	None	N
I/C	0.5087	ambiguous	0.4906	ambiguous	-0.569	Destabilizing	0.999	D	0.403	neutral	None	None	None	None	N
I/D	0.3903	ambiguous	0.3427	ambiguous	-0.168	Destabilizing	0.02	N	0.251	neutral	None	None	None	None	N
I/E	0.2887	likely_benign	0.2558	benign	-0.246	Destabilizing	0.759	D	0.431	neutral	None	None	None	None	N
I/F	0.0993	likely_benign	0.0935	benign	-0.65	Destabilizing	0.996	D	0.403	neutral	N	0.489478218	None	None	N
I/G	0.4565	ambiguous	0.4014	ambiguous	-0.926	Destabilizing	0.939	D	0.426	neutral	None	None	None	None	N
I/H	0.2548	likely_benign	0.223	benign	-0.234	Destabilizing	0.997	D	0.417	neutral	None	None	None	None	N
I/K	0.1837	likely_benign	0.1541	benign	-0.425	Destabilizing	0.884	D	0.427	neutral	None	None	None	None	N
I/L	0.0823	likely_benign	0.0821	benign	-0.323	Destabilizing	0.906	D	0.297	neutral	N	0.489420623	None	None	N
I/M	0.0866	likely_benign	0.0831	benign	-0.351	Destabilizing	0.996	D	0.423	neutral	D	0.531421961	None	None	N
I/N	0.1461	likely_benign	0.1237	benign	-0.173	Destabilizing	0.92	D	0.434	neutral	N	0.519319456	None	None	N
I/P	0.2591	likely_benign	0.2316	benign	-0.425	Destabilizing	0.997	D	0.43	neutral	None	None	None	None	N
I/Q	0.2263	likely_benign	0.1927	benign	-0.385	Destabilizing	0.982	D	0.427	neutral	None	None	None	None	N
I/R	0.147	likely_benign	0.1243	benign	0.112	Stabilizing	0.046	N	0.348	neutral	None	None	None	None	N
I/S	0.1956	likely_benign	0.1673	benign	-0.659	Destabilizing	0.92	D	0.398	neutral	N	0.504176645	None	None	N
I/T	0.1942	likely_benign	0.1578	benign	-0.626	Destabilizing	0.959	D	0.387	neutral	N	0.488439188	None	None	N
I/V	0.0793	likely_benign	0.0765	benign	-0.425	Destabilizing	0.906	D	0.309	neutral	N	0.450632949	None	None	N
I/W	0.5448	ambiguous	0.5127	ambiguous	-0.682	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
I/Y	0.2749	likely_benign	0.2638	benign	-0.432	Destabilizing	0.997	D	0.417	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.