TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26497	79714;79715;79716	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
N2AB	24856	74791;74792;74793	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
N2A	23929	72010;72011;72012	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
N2B	17432	52519;52520;52521	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
Novex-1	17557	52894;52895;52896	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
Novex-2	17624	53095;53096;53097	chr2:178566643;178566642;178566641	chr2:179431370;179431369;179431368
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: Fn3-81
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.417
• 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	0.001	N	0.221	0.036	0.37262878642	gnomAD-4.0.0	1.5934E-06	None	None	None	None	N	None	0	0	None	4.76735E-05	0	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
V/A	0.1274	likely_benign	0.1045	benign	-1.097	Destabilizing	0.001	N	0.16	neutral	N	0.479115124	None	None	N
V/C	0.6655	likely_pathogenic	0.5868	pathogenic	-0.635	Destabilizing	0.944	D	0.487	neutral	None	None	None	None	N
V/D	0.4394	ambiguous	0.3817	ambiguous	-1.059	Destabilizing	0.69	D	0.569	neutral	None	None	None	None	N
V/E	0.309	likely_benign	0.262	benign	-1.138	Destabilizing	0.627	D	0.494	neutral	N	0.464068314	None	None	N
V/F	0.1796	likely_benign	0.1519	benign	-1.087	Destabilizing	0.69	D	0.5	neutral	None	None	None	None	N
V/G	0.2561	likely_benign	0.1939	benign	-1.316	Destabilizing	0.193	N	0.501	neutral	N	0.466279903	None	None	N
V/H	0.5577	ambiguous	0.4686	ambiguous	-0.872	Destabilizing	0.981	D	0.571	neutral	None	None	None	None	N
V/I	0.0652	likely_benign	0.0642	benign	-0.631	Destabilizing	0.001	N	0.221	neutral	N	0.47580546	None	None	N
V/K	0.4019	ambiguous	0.324	benign	-1.006	Destabilizing	0.69	D	0.488	neutral	None	None	None	None	N
V/L	0.1326	likely_benign	0.1123	benign	-0.631	Destabilizing	0.001	N	0.157	neutral	N	0.456584981	None	None	N
V/M	0.1091	likely_benign	0.0962	benign	-0.388	Destabilizing	0.69	D	0.471	neutral	None	None	None	None	N
V/N	0.3066	likely_benign	0.2433	benign	-0.656	Destabilizing	0.818	D	0.573	neutral	None	None	None	None	N
V/P	0.7466	likely_pathogenic	0.6448	pathogenic	-0.751	Destabilizing	0.818	D	0.565	neutral	None	None	None	None	N
V/Q	0.3306	likely_benign	0.2609	benign	-0.921	Destabilizing	0.818	D	0.558	neutral	None	None	None	None	N
V/R	0.3705	ambiguous	0.2917	benign	-0.371	Destabilizing	0.69	D	0.573	neutral	None	None	None	None	N
V/S	0.1796	likely_benign	0.1448	benign	-1.032	Destabilizing	0.241	N	0.495	neutral	None	None	None	None	N
V/T	0.0984	likely_benign	0.0859	benign	-1.016	Destabilizing	0.008	N	0.213	neutral	None	None	None	None	N
V/W	0.7621	likely_pathogenic	0.6737	pathogenic	-1.207	Destabilizing	0.981	D	0.667	neutral	None	None	None	None	N
V/Y	0.5384	ambiguous	0.4622	ambiguous	-0.944	Destabilizing	0.818	D	0.5	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.