TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23650	71173;71174;71175	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
N2AB	22009	66250;66251;66252	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
N2A	21082	63469;63470;63471	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
N2B	14585	43978;43979;43980	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
Novex-1	14710	44353;44354;44355	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
Novex-2	14777	44554;44555;44556	chr2:178575184;178575183;178575182	chr2:179439911;179439910;179439909
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-130
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.6276
• 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
N/K	rs377185608	0.308	0.027	N	0.336	0.061	0.0986583533028	gnomAD-2.1.1	2.52E-05	None	None	None	None	N	None	2.07745E-04	2.85E-05	None	0	0	None	0	None	0	7.88E-06	0
N/K	rs377185608	0.308	0.027	N	0.336	0.061	0.0986583533028	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.44851E-04	0	0	0	0	None	0	0	1.47E-05	0	4.78011E-04
N/K	rs377185608	0.308	0.027	N	0.336	0.061	0.0986583533028	gnomAD-4.0.0	1.36425E-05	None	None	None	None	N	None	2.00326E-04	3.33979E-05	None	0	0	None	0	0	2.54377E-06	0	3.20461E-05

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
N/A	0.1879	likely_benign	0.2089	benign	-0.452	Destabilizing	0.149	N	0.354	neutral	None	None	None	None	N
N/C	0.228	likely_benign	0.244	benign	0.468	Stabilizing	0.935	D	0.481	neutral	None	None	None	None	N
N/D	0.1168	likely_benign	0.1288	benign	-0.443	Destabilizing	0.117	N	0.367	neutral	N	0.445124689	None	None	N
N/E	0.4143	ambiguous	0.4573	ambiguous	-0.45	Destabilizing	0.081	N	0.325	neutral	None	None	None	None	N
N/F	0.4907	ambiguous	0.5316	ambiguous	-0.677	Destabilizing	0.38	N	0.439	neutral	None	None	None	None	N
N/G	0.2525	likely_benign	0.2831	benign	-0.682	Destabilizing	0.067	N	0.321	neutral	None	None	None	None	N
N/H	0.0949	likely_benign	0.0949	benign	-0.758	Destabilizing	0.001	N	0.256	neutral	N	0.501423475	None	None	N
N/I	0.207	likely_benign	0.2418	benign	0.082	Stabilizing	0.484	N	0.439	neutral	N	0.470177849	None	None	N
N/K	0.3052	likely_benign	0.3263	benign	-0.043	Destabilizing	0.027	N	0.336	neutral	N	0.441759096	None	None	N
N/L	0.2341	likely_benign	0.2518	benign	0.082	Stabilizing	0.149	N	0.389	neutral	None	None	None	None	N
N/M	0.3191	likely_benign	0.3451	ambiguous	0.718	Stabilizing	0.935	D	0.402	neutral	None	None	None	None	N
N/P	0.3356	likely_benign	0.3461	ambiguous	-0.068	Destabilizing	0.555	D	0.411	neutral	None	None	None	None	N
N/Q	0.3055	likely_benign	0.3277	benign	-0.581	Destabilizing	0.38	N	0.331	neutral	None	None	None	None	N
N/R	0.3049	likely_benign	0.3355	benign	0.053	Stabilizing	None	N	0.121	neutral	None	None	None	None	N
N/S	0.0834	likely_benign	0.0862	benign	-0.297	Destabilizing	0.117	N	0.375	neutral	N	0.409779964	None	None	N
N/T	0.1075	likely_benign	0.1154	benign	-0.156	Destabilizing	0.211	N	0.305	neutral	N	0.416417935	None	None	N
N/V	0.1913	likely_benign	0.2223	benign	-0.068	Destabilizing	0.555	D	0.415	neutral	None	None	None	None	N
N/W	0.7853	likely_pathogenic	0.8163	pathogenic	-0.599	Destabilizing	0.935	D	0.573	neutral	None	None	None	None	N
N/Y	0.1852	likely_benign	0.2061	benign	-0.354	Destabilizing	0.188	N	0.411	neutral	N	0.507792087	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.