TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28024	84295;84296;84297	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
N2AB	26383	79372;79373;79374	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
N2A	25456	76591;76592;76593	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
N2B	18959	57100;57101;57102	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
Novex-1	19084	57475;57476;57477	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
Novex-2	19151	57676;57677;57678	chr2:178562062;178562061;178562060	chr2:179426789;179426788;179426787
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-142
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.5064
• 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	rs377540780	-0.417	0.002	N	0.183	0.06	0.0611884634855	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
E/D	rs377540780	-0.417	0.002	N	0.183	0.06	0.0611884634855	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	8.82E-05	0	0
E/D	rs377540780	-0.417	0.002	N	0.183	0.06	0.0611884634855	gnomAD-4.0.0	2.35544E-05	None	None	None	None	N	None	2.66994E-05	0	None	0	0	None	0	0	2.88221E-05	0	3.20318E-05
E/G	None	None	0.822	N	0.476	0.275	0.278143212241	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3239	likely_benign	0.3479	ambiguous	-0.549	Destabilizing	0.822	D	0.453	neutral	N	0.504597067	None	None	N
E/C	0.9412	likely_pathogenic	0.9496	pathogenic	-0.099	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
E/D	0.1076	likely_benign	0.1089	benign	-0.485	Destabilizing	0.002	N	0.183	neutral	N	0.4244987	None	None	N
E/F	0.8883	likely_pathogenic	0.8971	pathogenic	-0.374	Destabilizing	0.993	D	0.628	neutral	None	None	None	None	N
E/G	0.2724	likely_benign	0.289	benign	-0.782	Destabilizing	0.822	D	0.476	neutral	N	0.506501221	None	None	N
E/H	0.7484	likely_pathogenic	0.7767	pathogenic	-0.306	Destabilizing	0.993	D	0.395	neutral	None	None	None	None	N
E/I	0.7528	likely_pathogenic	0.7596	pathogenic	0.042	Stabilizing	0.978	D	0.617	neutral	None	None	None	None	N
E/K	0.4809	ambiguous	0.5139	ambiguous	0.142	Stabilizing	0.822	D	0.443	neutral	N	0.481218775	None	None	N
E/L	0.72	likely_pathogenic	0.7422	pathogenic	0.042	Stabilizing	0.978	D	0.592	neutral	None	None	None	None	N
E/M	0.7473	likely_pathogenic	0.7616	pathogenic	0.261	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	N
E/N	0.3489	ambiguous	0.3771	ambiguous	-0.21	Destabilizing	0.754	D	0.407	neutral	None	None	None	None	N
E/P	0.9353	likely_pathogenic	0.9405	pathogenic	-0.134	Destabilizing	0.978	D	0.422	neutral	None	None	None	None	N
E/Q	0.3529	ambiguous	0.377	ambiguous	-0.162	Destabilizing	0.904	D	0.4	neutral	N	0.49884453	None	None	N
E/R	0.6428	likely_pathogenic	0.6666	pathogenic	0.336	Stabilizing	0.978	D	0.393	neutral	None	None	None	None	N
E/S	0.3853	ambiguous	0.4117	ambiguous	-0.393	Destabilizing	0.86	D	0.41	neutral	None	None	None	None	N
E/T	0.4936	ambiguous	0.5287	ambiguous	-0.203	Destabilizing	0.86	D	0.417	neutral	None	None	None	None	N
E/V	0.5183	ambiguous	0.5417	ambiguous	-0.134	Destabilizing	0.97	D	0.489	neutral	N	0.486900648	None	None	N
E/W	0.9528	likely_pathogenic	0.9565	pathogenic	-0.191	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.7208	likely_pathogenic	0.7342	pathogenic	-0.128	Destabilizing	0.993	D	0.573	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.