TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8387	25384;25385;25386	chr2:178717715;178717714;178717713	chr2:179582442;179582441;179582440
N2AB	8070	24433;24434;24435	chr2:178717715;178717714;178717713	chr2:179582442;179582441;179582440
N2A	7143	21652;21653;21654	chr2:178717715;178717714;178717713	chr2:179582442;179582441;179582440
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-69
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7762
• Predicted PPI site: I

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/G	None	None	0.855	N	0.327	0.149	0.185906805712	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85963E-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	0.1341	likely_benign	0.1458	benign	-0.03	Destabilizing	0.046	N	0.101	neutral	N	0.44193995	None	None	I
E/C	0.8955	likely_pathogenic	0.9155	pathogenic	-0.184	Destabilizing	0.999	D	0.417	neutral	None	None	None	None	I
E/D	0.1369	likely_benign	0.171	benign	-0.338	Destabilizing	0.314	N	0.375	neutral	N	0.472646859	None	None	I
E/F	0.7296	likely_pathogenic	0.7951	pathogenic	0.009	Stabilizing	0.998	D	0.436	neutral	None	None	None	None	I
E/G	0.1946	likely_benign	0.2393	benign	-0.162	Destabilizing	0.855	D	0.327	neutral	N	0.469318552	None	None	I
E/H	0.4887	ambiguous	0.5584	ambiguous	0.613	Stabilizing	0.997	D	0.377	neutral	None	None	None	None	I
E/I	0.379	ambiguous	0.425	ambiguous	0.265	Stabilizing	0.986	D	0.475	neutral	None	None	None	None	I
E/K	0.149	likely_benign	0.1783	benign	0.485	Stabilizing	0.941	D	0.351	neutral	N	0.463566016	None	None	I
E/L	0.3685	ambiguous	0.4436	ambiguous	0.265	Stabilizing	0.908	D	0.479	neutral	None	None	None	None	I
E/M	0.464	ambiguous	0.5119	ambiguous	0.037	Stabilizing	0.993	D	0.414	neutral	None	None	None	None	I
E/N	0.2857	likely_benign	0.348	ambiguous	0.122	Stabilizing	0.821	D	0.423	neutral	None	None	None	None	I
E/P	0.3775	ambiguous	0.5161	ambiguous	0.185	Stabilizing	0.005	N	0.162	neutral	None	None	None	None	I
E/Q	0.132	likely_benign	0.1424	benign	0.149	Stabilizing	0.958	D	0.461	neutral	N	0.447847202	None	None	I
E/R	0.2717	likely_benign	0.3302	benign	0.738	Stabilizing	0.977	D	0.407	neutral	None	None	None	None	I
E/S	0.1786	likely_benign	0.1999	benign	0.012	Stabilizing	0.307	N	0.154	neutral	None	None	None	None	I
E/T	0.2483	likely_benign	0.2797	benign	0.132	Stabilizing	0.887	D	0.359	neutral	None	None	None	None	I
E/V	0.2216	likely_benign	0.2447	benign	0.185	Stabilizing	0.841	D	0.454	neutral	N	0.488251029	None	None	I
E/W	0.9072	likely_pathogenic	0.9425	pathogenic	0.083	Stabilizing	1.0	D	0.517	neutral	None	None	None	None	I
E/Y	0.6041	likely_pathogenic	0.6859	pathogenic	0.243	Stabilizing	0.999	D	0.428	neutral	None	None	None	None	I

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.