TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2179	6760;6761;6762	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
N2AB	2179	6760;6761;6762	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
N2A	2179	6760;6761;6762	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
N2B	2133	6622;6623;6624	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
Novex-1	2133	6622;6623;6624	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
Novex-2	2133	6622;6623;6624	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901
Novex-3	2179	6760;6761;6762	chr2:178775176;178775175;178775174	chr2:179639903;179639902;179639901

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-11
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6712
• 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/V	None	None	0.126	N	0.311	0.272	0.466991082792	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	2.775E-05	None	0	0	0	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	0.0897	likely_benign	0.0838	benign	-0.82	Destabilizing	0.001	N	0.131	neutral	N	0.49697326	None	None	N
E/C	0.7074	likely_pathogenic	0.6661	pathogenic	-0.368	Destabilizing	0.987	D	0.263	neutral	None	None	None	None	N
E/D	0.1345	likely_benign	0.1276	benign	-0.666	Destabilizing	0.126	N	0.221	neutral	N	0.512583814	None	None	N
E/F	0.5956	likely_pathogenic	0.5765	pathogenic	-0.208	Destabilizing	0.868	D	0.34	neutral	None	None	None	None	N
E/G	0.1314	likely_benign	0.1208	benign	-1.137	Destabilizing	0.126	N	0.283	neutral	N	0.48749084	None	None	N
E/H	0.3049	likely_benign	0.2932	benign	-0.239	Destabilizing	0.003	N	0.159	neutral	None	None	None	None	N
E/I	0.2146	likely_benign	0.2123	benign	0.032	Stabilizing	0.481	N	0.413	neutral	None	None	None	None	N
E/K	0.0893	likely_benign	0.0966	benign	-0.177	Destabilizing	0.001	N	0.117	neutral	N	0.475875119	None	None	N
E/L	0.2302	likely_benign	0.2225	benign	0.032	Stabilizing	0.276	N	0.336	neutral	None	None	None	None	N
E/M	0.257	likely_benign	0.2581	benign	0.316	Stabilizing	0.868	D	0.279	neutral	None	None	None	None	N
E/N	0.1552	likely_benign	0.1429	benign	-0.705	Destabilizing	0.001	N	0.095	neutral	None	None	None	None	N
E/P	0.2285	likely_benign	0.2154	benign	-0.231	Destabilizing	0.003	N	0.157	neutral	None	None	None	None	N
E/Q	0.0913	likely_benign	0.0878	benign	-0.599	Destabilizing	0.009	N	0.141	neutral	N	0.504974046	None	None	N
E/R	0.1712	likely_benign	0.1797	benign	0.15	Stabilizing	0.16	N	0.201	neutral	None	None	None	None	N
E/S	0.1383	likely_benign	0.1242	benign	-0.959	Destabilizing	0.077	N	0.162	neutral	None	None	None	None	N
E/T	0.1299	likely_benign	0.1239	benign	-0.688	Destabilizing	0.005	N	0.134	neutral	None	None	None	None	N
E/V	0.1282	likely_benign	0.1257	benign	-0.231	Destabilizing	0.126	N	0.311	neutral	N	0.507393203	None	None	N
E/W	0.8422	likely_pathogenic	0.8337	pathogenic	0.129	Stabilizing	0.987	D	0.271	neutral	None	None	None	None	N
E/Y	0.4541	ambiguous	0.4359	ambiguous	0.076	Stabilizing	0.764	D	0.378	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.