TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31112	93559;93560;93561	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
N2AB	29471	88636;88637;88638	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
N2A	28544	85855;85856;85857	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
N2B	22047	66364;66365;66366	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
Novex-1	22172	66739;66740;66741	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
Novex-2	22239	66940;66941;66942	chr2:178548292;178548291;178548290	chr2:179413019;179413018;179413017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-114
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.5613
• 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
E/D	None	None	0.997	N	0.531	0.088	0.211220785272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs367766603	0.676	0.997	N	0.684	0.308	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs367766603	0.676	0.997	N	0.684	0.308	None	gnomAD-4.0.0	1.36835E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79888E-06	0	0
E/Q	None	None	0.999	N	0.637	0.208	0.220303561663	gnomAD-4.0.0	6.84177E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99439E-07	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
E/A	0.3845	ambiguous	0.2414	benign	-0.161	Destabilizing	0.997	D	0.737	deleterious	N	0.493385569	None	None	N
E/C	0.9647	likely_pathogenic	0.9384	pathogenic	0.042	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/D	0.5372	ambiguous	0.4361	ambiguous	-0.314	Destabilizing	0.997	D	0.531	neutral	N	0.465873681	None	None	N
E/F	0.9789	likely_pathogenic	0.9504	pathogenic	-0.212	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/G	0.4821	ambiguous	0.3193	benign	-0.308	Destabilizing	0.999	D	0.611	neutral	N	0.50760566	None	None	N
E/H	0.9131	likely_pathogenic	0.8218	pathogenic	0.131	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/I	0.8952	likely_pathogenic	0.7859	pathogenic	0.175	Stabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/K	0.5909	likely_pathogenic	0.3817	ambiguous	0.485	Stabilizing	0.997	D	0.684	prob.delet.	N	0.516803934	None	None	N
E/L	0.8683	likely_pathogenic	0.7338	pathogenic	0.175	Stabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	N
E/M	0.8419	likely_pathogenic	0.7	pathogenic	0.154	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/N	0.7757	likely_pathogenic	0.648	pathogenic	0.25	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/P	0.9926	likely_pathogenic	0.9853	pathogenic	0.082	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/Q	0.2912	likely_benign	0.1848	benign	0.257	Stabilizing	0.999	D	0.637	neutral	N	0.472898441	None	None	N
E/R	0.7073	likely_pathogenic	0.511	ambiguous	0.625	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/S	0.5029	ambiguous	0.3409	ambiguous	0.12	Stabilizing	0.998	D	0.738	deleterious	None	None	None	None	N
E/T	0.6789	likely_pathogenic	0.4812	ambiguous	0.24	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/V	0.721	likely_pathogenic	0.5287	ambiguous	0.082	Stabilizing	0.999	D	0.709	prob.delet.	N	0.476618569	None	None	N
E/W	0.9948	likely_pathogenic	0.9871	pathogenic	-0.143	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/Y	0.9628	likely_pathogenic	0.9219	pathogenic	0.018	Stabilizing	1.0	D	0.762	deleterious	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.