TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29971	90136;90137;90138	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
N2AB	28330	85213;85214;85215	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
N2A	27403	82432;82433;82434	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
N2B	20906	62941;62942;62943	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
Novex-1	21031	63316;63317;63318	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
Novex-2	21098	63517;63518;63519	chr2:178552989;178552988;178552987	chr2:179417716;179417715;179417714
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: Fn3-106
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1568
• 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/G	rs1361724655	-2.058	0.946	D	0.751	0.476	0.470237251169	gnomAD-4.0.0	1.59536E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	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	0.8059	likely_pathogenic	0.7495	pathogenic	-1.058	Destabilizing	0.716	D	0.663	neutral	D	0.530583075	None	None	N
E/C	0.9837	likely_pathogenic	0.9767	pathogenic	-0.222	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
E/D	0.784	likely_pathogenic	0.7392	pathogenic	-1.435	Destabilizing	0.834	D	0.628	neutral	N	0.481625908	None	None	N
E/F	0.9886	likely_pathogenic	0.9841	pathogenic	-0.696	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
E/G	0.8662	likely_pathogenic	0.8148	pathogenic	-1.473	Destabilizing	0.946	D	0.751	deleterious	D	0.539105451	None	None	N
E/H	0.9524	likely_pathogenic	0.9414	pathogenic	-0.57	Destabilizing	0.989	D	0.837	deleterious	None	None	None	None	N
E/I	0.964	likely_pathogenic	0.9506	pathogenic	0.13	Stabilizing	0.979	D	0.822	deleterious	None	None	None	None	N
E/K	0.8729	likely_pathogenic	0.8562	pathogenic	-0.867	Destabilizing	0.716	D	0.65	neutral	N	0.517959322	None	None	N
E/L	0.9407	likely_pathogenic	0.9243	pathogenic	0.13	Stabilizing	0.959	D	0.797	deleterious	None	None	None	None	N
E/M	0.9295	likely_pathogenic	0.9129	pathogenic	0.797	Stabilizing	0.994	D	0.813	deleterious	None	None	None	None	N
E/N	0.9416	likely_pathogenic	0.9226	pathogenic	-1.184	Destabilizing	0.959	D	0.819	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9992	pathogenic	-0.25	Destabilizing	0.979	D	0.798	deleterious	None	None	None	None	N
E/Q	0.3369	likely_benign	0.307	benign	-0.873	Destabilizing	0.035	N	0.362	neutral	N	0.517076079	None	None	N
E/R	0.9186	likely_pathogenic	0.903	pathogenic	-0.798	Destabilizing	0.921	D	0.82	deleterious	None	None	None	None	N
E/S	0.821	likely_pathogenic	0.765	pathogenic	-1.805	Destabilizing	0.769	D	0.699	prob.neutral	None	None	None	None	N
E/T	0.9267	likely_pathogenic	0.9074	pathogenic	-1.405	Destabilizing	0.959	D	0.773	deleterious	None	None	None	None	N
E/V	0.9034	likely_pathogenic	0.8814	pathogenic	-0.25	Destabilizing	0.946	D	0.781	deleterious	D	0.531343543	None	None	N
E/W	0.9965	likely_pathogenic	0.9948	pathogenic	-0.779	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
E/Y	0.9832	likely_pathogenic	0.9774	pathogenic	-0.459	Destabilizing	0.979	D	0.815	deleterious	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.