TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7368	22327;22328;22329	chr2:178722797;178722796;178722795	chr2:179587524;179587523;179587522
N2AB	7051	21376;21377;21378	chr2:178722797;178722796;178722795	chr2:179587524;179587523;179587522
N2A	6124	18595;18596;18597	chr2:178722797;178722796;178722795	chr2:179587524;179587523;179587522
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-58
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.4722
• 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/A	rs1420368632	-0.715	0.454	N	0.292	0.078	0.18995819373	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/A	rs1420368632	-0.715	0.454	N	0.292	0.078	0.18995819373	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs1420368632	-0.715	0.454	N	0.292	0.078	0.18995819373	gnomAD-4.0.0	8.6782E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18687E-05	0	0
E/Q	None	None	0.801	N	0.381	0.162	0.132336055621	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
E/A	0.089	likely_benign	0.1213	benign	-0.828	Destabilizing	0.454	N	0.292	neutral	N	0.417439442	None	None	N
E/C	0.7672	likely_pathogenic	0.901	pathogenic	-0.391	Destabilizing	0.998	D	0.351	neutral	None	None	None	None	N
E/D	0.0821	likely_benign	0.1165	benign	-0.641	Destabilizing	0.454	N	0.302	neutral	N	0.372379156	None	None	N
E/F	0.5832	likely_pathogenic	0.7768	pathogenic	-0.386	Destabilizing	0.991	D	0.377	neutral	None	None	None	None	N
E/G	0.1068	likely_benign	0.1619	benign	-1.113	Destabilizing	0.005	N	0.199	neutral	N	0.412340266	None	None	N
E/H	0.3203	likely_benign	0.5011	ambiguous	-0.374	Destabilizing	0.974	D	0.327	neutral	None	None	None	None	N
E/I	0.2638	likely_benign	0.4213	ambiguous	-0.072	Destabilizing	0.949	D	0.414	neutral	None	None	None	None	N
E/K	0.1285	likely_benign	0.2085	benign	-0.343	Destabilizing	0.051	N	0.115	neutral	N	0.347672712	None	None	N
E/L	0.28	likely_benign	0.4386	ambiguous	-0.072	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
E/M	0.366	ambiguous	0.5145	ambiguous	0.216	Stabilizing	0.998	D	0.323	neutral	None	None	None	None	N
E/N	0.1425	likely_benign	0.2434	benign	-0.759	Destabilizing	0.067	N	0.103	neutral	None	None	None	None	N
E/P	0.455	ambiguous	0.72	pathogenic	-0.303	Destabilizing	0.991	D	0.409	neutral	None	None	None	None	N
E/Q	0.1129	likely_benign	0.1557	benign	-0.657	Destabilizing	0.801	D	0.381	neutral	N	0.427579078	None	None	N
E/R	0.2043	likely_benign	0.3379	benign	-0.01	Destabilizing	0.728	D	0.265	neutral	None	None	None	None	N
E/S	0.1142	likely_benign	0.1764	benign	-0.985	Destabilizing	0.525	D	0.281	neutral	None	None	None	None	N
E/T	0.1391	likely_benign	0.215	benign	-0.751	Destabilizing	0.029	N	0.137	neutral	None	None	None	None	N
E/V	0.1712	likely_benign	0.267	benign	-0.303	Destabilizing	0.801	D	0.349	neutral	N	0.432966255	None	None	N
E/W	0.8009	likely_pathogenic	0.922	pathogenic	-0.122	Destabilizing	0.998	D	0.412	neutral	None	None	None	None	N
E/Y	0.4496	ambiguous	0.656	pathogenic	-0.148	Destabilizing	0.991	D	0.347	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.