TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6968	21127;21128;21129	chr2:178724473;178724472;178724471	chr2:179589200;179589199;179589198
N2AB	6651	20176;20177;20178	chr2:178724473;178724472;178724471	chr2:179589200;179589199;179589198
N2A	5724	17395;17396;17397	chr2:178724473;178724472;178724471	chr2:179589200;179589199;179589198
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-54
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5876
• 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	None	None	1.0	D	0.729	0.607	0.735594876934	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.3024	likely_benign	0.2937	benign	-0.812	Destabilizing	0.999	D	0.687	prob.neutral	N	0.508721247	None	None	N
E/C	0.9485	likely_pathogenic	0.9503	pathogenic	-0.188	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/D	0.3387	likely_benign	0.2696	benign	-0.855	Destabilizing	0.999	D	0.531	neutral	N	0.496600099	None	None	N
E/F	0.8869	likely_pathogenic	0.8808	pathogenic	-0.631	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/G	0.4219	ambiguous	0.3979	ambiguous	-1.1	Destabilizing	1.0	D	0.729	prob.delet.	D	0.535889206	None	None	N
E/H	0.6995	likely_pathogenic	0.6929	pathogenic	-0.825	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/I	0.5791	likely_pathogenic	0.57	pathogenic	-0.052	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/K	0.3954	ambiguous	0.4157	ambiguous	-0.141	Destabilizing	0.999	D	0.62	neutral	N	0.455233479	None	None	N
E/L	0.6723	likely_pathogenic	0.6558	pathogenic	-0.052	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/M	0.6853	likely_pathogenic	0.6871	pathogenic	0.423	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/N	0.573	likely_pathogenic	0.5175	ambiguous	-0.534	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/P	0.9729	likely_pathogenic	0.9391	pathogenic	-0.285	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.1963	likely_benign	0.2015	benign	-0.478	Destabilizing	1.0	D	0.679	prob.neutral	N	0.48978877	None	None	N
E/R	0.5229	ambiguous	0.5429	ambiguous	-0.009	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/S	0.3822	ambiguous	0.3564	ambiguous	-0.778	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
E/T	0.375	ambiguous	0.3627	ambiguous	-0.537	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/V	0.3651	ambiguous	0.361	ambiguous	-0.285	Destabilizing	1.0	D	0.751	deleterious	N	0.503200784	None	None	N
E/W	0.9608	likely_pathogenic	0.9588	pathogenic	-0.425	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.8365	likely_pathogenic	0.8192	pathogenic	-0.37	Destabilizing	1.0	D	0.765	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.