TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19356	58291;58292;58293	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
N2AB	17715	53368;53369;53370	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
N2A	16788	50587;50588;50589	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
N2B	10291	31096;31097;31098	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
Novex-1	10416	31471;31472;31473	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
Novex-2	10483	31672;31673;31674	chr2:178594428;178594427;178594426	chr2:179459155;179459154;179459153
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: Fn3-28
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1436
• 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/D	None	None	0.999	N	0.602	0.309	0.368369118721	gnomAD-4.0.0	8.40229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18756E-06	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	0.8863	likely_pathogenic	0.8696	pathogenic	-1.392	Destabilizing	0.999	D	0.68	prob.neutral	N	0.482297471	None	None	N
E/C	0.9811	likely_pathogenic	0.9817	pathogenic	-0.535	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/D	0.9357	likely_pathogenic	0.9205	pathogenic	-1.567	Destabilizing	0.999	D	0.602	neutral	N	0.4886538	None	None	N
E/F	0.9898	likely_pathogenic	0.9861	pathogenic	-0.97	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.9471	likely_pathogenic	0.9354	pathogenic	-1.818	Destabilizing	1.0	D	0.723	prob.delet.	N	0.50404903	None	None	N
E/H	0.9856	likely_pathogenic	0.9835	pathogenic	-0.882	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/I	0.934	likely_pathogenic	0.9311	pathogenic	-0.169	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.9719	likely_pathogenic	0.9689	pathogenic	-1.129	Destabilizing	0.999	D	0.629	neutral	D	0.524138125	None	None	N
E/L	0.9673	likely_pathogenic	0.9629	pathogenic	-0.169	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/M	0.9538	likely_pathogenic	0.949	pathogenic	0.573	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/N	0.9791	likely_pathogenic	0.9734	pathogenic	-1.463	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9989	pathogenic	-0.561	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/Q	0.7433	likely_pathogenic	0.7336	pathogenic	-1.161	Destabilizing	1.0	D	0.694	prob.neutral	N	0.501146622	None	None	N
E/R	0.9688	likely_pathogenic	0.9654	pathogenic	-1.009	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/S	0.9129	likely_pathogenic	0.9003	pathogenic	-2.127	Highly Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/T	0.9435	likely_pathogenic	0.9369	pathogenic	-1.714	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/V	0.894	likely_pathogenic	0.8843	pathogenic	-0.561	Destabilizing	1.0	D	0.71	prob.delet.	D	0.525119559	None	None	N
E/W	0.9976	likely_pathogenic	0.9966	pathogenic	-0.964	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/Y	0.9852	likely_pathogenic	0.9799	pathogenic	-0.722	Destabilizing	1.0	D	0.751	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.