TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2981	9166;9167;9168	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
N2AB	2981	9166;9167;9168	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
N2A	2981	9166;9167;9168	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
N2B	2935	9028;9029;9030	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
Novex-1	2935	9028;9029;9030	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
Novex-2	2935	9028;9029;9030	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620
Novex-3	2981	9166;9167;9168	chr2:178768895;178768894;178768893	chr2:179633622;179633621;179633620

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-20
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.3292
• 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/K	None	None	0.956	N	0.559	0.349	0.398133443147	gnomAD-4.0.0	6.84132E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99305E-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	0.4916	ambiguous	0.3847	ambiguous	-0.348	Destabilizing	0.978	D	0.588	neutral	N	0.439430724	None	None	N
E/C	0.985	likely_pathogenic	0.9822	pathogenic	0.035	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/D	0.8064	likely_pathogenic	0.6715	pathogenic	-0.408	Destabilizing	0.948	D	0.515	neutral	N	0.48601087	None	None	N
E/F	0.9774	likely_pathogenic	0.9662	pathogenic	-0.31	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
E/G	0.6671	likely_pathogenic	0.5429	ambiguous	-0.563	Destabilizing	0.989	D	0.601	neutral	N	0.501713739	None	None	N
E/H	0.9452	likely_pathogenic	0.9155	pathogenic	-0.241	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
E/I	0.8771	likely_pathogenic	0.8095	pathogenic	0.187	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
E/K	0.4938	ambiguous	0.4058	ambiguous	0.198	Stabilizing	0.956	D	0.559	neutral	N	0.391469994	None	None	N
E/L	0.8721	likely_pathogenic	0.7936	pathogenic	0.187	Stabilizing	0.995	D	0.615	neutral	None	None	None	None	N
E/M	0.8215	likely_pathogenic	0.7662	pathogenic	0.357	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/N	0.8967	likely_pathogenic	0.8297	pathogenic	-0.006	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
E/P	0.9647	likely_pathogenic	0.934	pathogenic	0.029	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	N
E/Q	0.3898	ambiguous	0.3333	benign	0.019	Stabilizing	0.63	D	0.298	neutral	N	0.433174037	None	None	N
E/R	0.6943	likely_pathogenic	0.5975	pathogenic	0.365	Stabilizing	0.983	D	0.554	neutral	None	None	None	None	N
E/S	0.7535	likely_pathogenic	0.65	pathogenic	-0.206	Destabilizing	0.983	D	0.56	neutral	None	None	None	None	N
E/T	0.7686	likely_pathogenic	0.6591	pathogenic	-0.041	Destabilizing	0.992	D	0.578	neutral	None	None	None	None	N
E/V	0.675	likely_pathogenic	0.5608	ambiguous	0.029	Stabilizing	0.997	D	0.59	neutral	N	0.44602831	None	None	N
E/W	0.9942	likely_pathogenic	0.9901	pathogenic	-0.203	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/Y	0.9729	likely_pathogenic	0.9578	pathogenic	-0.08	Destabilizing	0.999	D	0.661	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.