TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24367	73324;73325;73326	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
N2AB	22726	68401;68402;68403	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
N2A	21799	65620;65621;65622	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
N2B	15302	46129;46130;46131	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
Novex-1	15427	46504;46505;46506	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
Novex-2	15494	46705;46706;46707	chr2:178573033;178573032;178573031	chr2:179437760;179437759;179437758
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: Fn3-65
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4362
• 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/A	None	None	0.058	N	0.298	0.137	0.19670166235	gnomAD-4.0.0	6.84487E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99675E-07	0	0
E/D	rs1357419691	-0.413	0.822	N	0.317	0.086	0.290590437066	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1357419691	-0.413	0.822	N	0.317	0.086	0.290590437066	gnomAD-4.0.0	3.18567E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-05	3.02737E-05
E/V	None	None	0.698	N	0.382	0.248	0.352262096564	gnomAD-4.0.0	1.36897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79935E-06	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	0.1018	likely_benign	0.1027	benign	-0.421	Destabilizing	0.058	N	0.298	neutral	N	0.472255362	None	None	N
E/C	0.6913	likely_pathogenic	0.6828	pathogenic	-0.122	Destabilizing	0.998	D	0.614	neutral	None	None	None	None	N
E/D	0.0929	likely_benign	0.0993	benign	-0.462	Destabilizing	0.822	D	0.317	neutral	N	0.472388648	None	None	N
E/F	0.6526	likely_pathogenic	0.6514	pathogenic	-0.269	Destabilizing	0.978	D	0.587	neutral	None	None	None	None	N
E/G	0.0925	likely_benign	0.0916	benign	-0.654	Destabilizing	0.822	D	0.393	neutral	N	0.481045416	None	None	N
E/H	0.3304	likely_benign	0.3381	benign	-0.212	Destabilizing	0.998	D	0.323	neutral	None	None	None	None	N
E/I	0.2604	likely_benign	0.2781	benign	0.17	Stabilizing	0.956	D	0.58	neutral	None	None	None	None	N
E/K	0.0878	likely_benign	0.09	benign	0.004	Stabilizing	0.822	D	0.321	neutral	N	0.509696242	None	None	N
E/L	0.2927	likely_benign	0.2982	benign	0.17	Stabilizing	0.754	D	0.455	neutral	None	None	None	None	N
E/M	0.2975	likely_benign	0.3065	benign	0.301	Stabilizing	0.998	D	0.51	neutral	None	None	None	None	N
E/N	0.1397	likely_benign	0.1493	benign	-0.221	Destabilizing	0.956	D	0.339	neutral	None	None	None	None	N
E/P	0.6573	likely_pathogenic	0.6581	pathogenic	-0.006	Destabilizing	0.978	D	0.403	neutral	None	None	None	None	N
E/Q	0.1135	likely_benign	0.1145	benign	-0.165	Destabilizing	0.97	D	0.355	neutral	N	0.512736547	None	None	N
E/R	0.1778	likely_benign	0.1769	benign	0.229	Stabilizing	0.956	D	0.345	neutral	None	None	None	None	N
E/S	0.1264	likely_benign	0.1292	benign	-0.425	Destabilizing	0.754	D	0.287	neutral	None	None	None	None	N
E/T	0.1249	likely_benign	0.1322	benign	-0.243	Destabilizing	0.019	N	0.303	neutral	None	None	None	None	N
E/V	0.1518	likely_benign	0.1574	benign	-0.006	Destabilizing	0.698	D	0.382	neutral	N	0.497980526	None	None	N
E/W	0.8196	likely_pathogenic	0.8148	pathogenic	-0.135	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
E/Y	0.4826	ambiguous	0.4837	ambiguous	-0.045	Destabilizing	0.993	D	0.495	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.