TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2995	9208;9209;9210	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
N2AB	2995	9208;9209;9210	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
N2A	2995	9208;9209;9210	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
N2B	2949	9070;9071;9072	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
Novex-1	2949	9070;9071;9072	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
Novex-2	2949	9070;9071;9072	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578
Novex-3	2995	9208;9209;9210	chr2:178768853;178768852;178768851	chr2:179633580;179633579;179633578

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-20
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.3991
• 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	0.999	N	0.531	0.367	0.266385636622	gnomAD-4.0.0	6.84098E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.993E-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	0.3317	likely_benign	0.4127	ambiguous	-0.27	Destabilizing	0.999	D	0.727	prob.delet.	N	0.509023002	None	None	N
E/C	0.9668	likely_pathogenic	0.9816	pathogenic	-0.285	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/D	0.3224	likely_benign	0.3676	ambiguous	-0.419	Destabilizing	0.999	D	0.531	neutral	N	0.480281456	None	None	N
E/F	0.969	likely_pathogenic	0.9818	pathogenic	0.047	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/G	0.4832	ambiguous	0.5808	pathogenic	-0.484	Destabilizing	1.0	D	0.677	prob.neutral	N	0.514793076	None	None	N
E/H	0.8267	likely_pathogenic	0.8842	pathogenic	0.496	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/I	0.7789	likely_pathogenic	0.8563	pathogenic	0.266	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/K	0.3153	likely_benign	0.4247	ambiguous	0.321	Stabilizing	0.999	D	0.725	prob.delet.	N	0.504903406	None	None	N
E/L	0.7803	likely_pathogenic	0.8518	pathogenic	0.266	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
E/M	0.8222	likely_pathogenic	0.8821	pathogenic	0.111	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.6222	likely_pathogenic	0.7158	pathogenic	-0.212	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/P	0.6726	likely_pathogenic	0.752	pathogenic	0.108	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/Q	0.3213	likely_benign	0.3978	ambiguous	-0.142	Destabilizing	1.0	D	0.689	prob.neutral	D	0.540725268	None	None	N
E/R	0.5514	ambiguous	0.6528	pathogenic	0.679	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/S	0.4479	ambiguous	0.5298	ambiguous	-0.339	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
E/T	0.5131	ambiguous	0.6171	pathogenic	-0.153	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/V	0.5651	likely_pathogenic	0.6803	pathogenic	0.108	Stabilizing	1.0	D	0.728	prob.delet.	N	0.505116094	None	None	N
E/W	0.9892	likely_pathogenic	0.9933	pathogenic	0.234	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/Y	0.9311	likely_pathogenic	0.9581	pathogenic	0.304	Stabilizing	1.0	D	0.717	prob.delet.	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.