TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23752	71479;71480;71481	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
N2AB	22111	66556;66557;66558	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
N2A	21184	63775;63776;63777	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
N2B	14687	44284;44285;44286	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
Novex-1	14812	44659;44660;44661	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
Novex-2	14879	44860;44861;44862	chr2:178574878;178574877;178574876	chr2:179439605;179439604;179439603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-60
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.8152
• 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/K	rs1709511196	None	0.014	N	0.191	0.183	0.311387274539	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1709511196	None	0.014	N	0.191	0.183	0.311387274539	gnomAD-4.0.0	6.57678E-06	None	None	None	None	N	None	0	6.55136E-05	None	0	0	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	0.0982	likely_benign	0.0871	benign	-0.046	Destabilizing	0.698	D	0.481	neutral	N	0.459259927	None	None	N
E/C	0.6859	likely_pathogenic	0.6013	pathogenic	-0.045	Destabilizing	0.998	D	0.614	neutral	None	None	None	None	N
E/D	0.1457	likely_benign	0.1294	benign	-0.188	Destabilizing	0.698	D	0.489	neutral	N	0.495508729	None	None	N
E/F	0.6389	likely_pathogenic	0.5478	ambiguous	-0.109	Destabilizing	0.956	D	0.578	neutral	None	None	None	None	N
E/G	0.1417	likely_benign	0.1234	benign	-0.176	Destabilizing	0.822	D	0.547	neutral	N	0.490892343	None	None	N
E/H	0.3695	ambiguous	0.3129	benign	0.379	Stabilizing	0.978	D	0.469	neutral	None	None	None	None	N
E/I	0.1698	likely_benign	0.1406	benign	0.238	Stabilizing	0.915	D	0.584	neutral	None	None	None	None	N
E/K	0.0843	likely_benign	0.0745	benign	0.446	Stabilizing	0.014	N	0.191	neutral	N	0.464761747	None	None	N
E/L	0.1993	likely_benign	0.1565	benign	0.238	Stabilizing	0.019	N	0.359	neutral	None	None	None	None	N
E/M	0.2724	likely_benign	0.2205	benign	0.095	Stabilizing	0.988	D	0.558	neutral	None	None	None	None	N
E/N	0.2148	likely_benign	0.1797	benign	0.296	Stabilizing	0.16	N	0.189	neutral	None	None	None	None	N
E/P	0.4188	ambiguous	0.3546	ambiguous	0.162	Stabilizing	0.978	D	0.515	neutral	None	None	None	None	N
E/Q	0.102	likely_benign	0.0915	benign	0.298	Stabilizing	0.822	D	0.504	neutral	N	0.514614564	None	None	N
E/R	0.1649	likely_benign	0.145	benign	0.644	Stabilizing	0.754	D	0.501	neutral	None	None	None	None	N
E/S	0.148	likely_benign	0.1266	benign	0.121	Stabilizing	0.86	D	0.489	neutral	None	None	None	None	N
E/T	0.1411	likely_benign	0.1209	benign	0.227	Stabilizing	0.86	D	0.529	neutral	None	None	None	None	N
E/V	0.111	likely_benign	0.0974	benign	0.162	Stabilizing	0.698	D	0.528	neutral	N	0.497183597	None	None	N
E/W	0.8322	likely_pathogenic	0.7643	pathogenic	-0.062	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.5318	ambiguous	0.4525	ambiguous	0.118	Stabilizing	0.978	D	0.567	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.