TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29100	87523;87524;87525	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
N2AB	27459	82600;82601;82602	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
N2A	26532	79819;79820;79821	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
N2B	20035	60328;60329;60330	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
Novex-1	20160	60703;60704;60705	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
Novex-2	20227	60904;60905;60906	chr2:178558056;178558055;178558054	chr2:179422783;179422782;179422781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-145
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1559
• 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
L/M	rs1702186822	None	0.81	N	0.729	0.121	0.373357554552	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/M	rs1702186822	None	0.81	N	0.729	0.121	0.373357554552	gnomAD-4.0.0	6.57108E-06	None	None	None	None	N	None	2.41266E-05	0	None	0	0	None	0	0	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
L/A	0.5807	likely_pathogenic	0.5232	ambiguous	-2.913	Highly Destabilizing	0.25	N	0.669	neutral	None	None	None	None	N
L/C	0.5791	likely_pathogenic	0.508	ambiguous	-2.63	Highly Destabilizing	0.977	D	0.666	neutral	None	None	None	None	N
L/D	0.9943	likely_pathogenic	0.9911	pathogenic	-3.33	Highly Destabilizing	0.972	D	0.763	deleterious	None	None	None	None	N
L/E	0.9712	likely_pathogenic	0.9637	pathogenic	-3.112	Highly Destabilizing	0.92	D	0.761	deleterious	None	None	None	None	N
L/F	0.2807	likely_benign	0.1833	benign	-1.881	Destabilizing	0.012	N	0.539	neutral	None	None	None	None	N
L/G	0.9253	likely_pathogenic	0.9036	pathogenic	-3.471	Highly Destabilizing	0.92	D	0.771	deleterious	None	None	None	None	N
L/H	0.8905	likely_pathogenic	0.8233	pathogenic	-2.877	Highly Destabilizing	0.992	D	0.729	prob.delet.	None	None	None	None	N
L/I	0.0859	likely_benign	0.0847	benign	-1.295	Destabilizing	0.009	N	0.392	neutral	None	None	None	None	N
L/K	0.9631	likely_pathogenic	0.9387	pathogenic	-2.442	Highly Destabilizing	0.92	D	0.737	prob.delet.	None	None	None	None	N
L/M	0.1239	likely_benign	0.1058	benign	-1.382	Destabilizing	0.81	D	0.729	prob.delet.	N	0.45842206	None	None	N
L/N	0.9581	likely_pathogenic	0.9357	pathogenic	-2.814	Highly Destabilizing	0.972	D	0.752	deleterious	None	None	None	None	N
L/P	0.9909	likely_pathogenic	0.9876	pathogenic	-1.816	Destabilizing	0.963	D	0.761	deleterious	N	0.477007821	None	None	N
L/Q	0.8888	likely_pathogenic	0.8482	pathogenic	-2.696	Highly Destabilizing	0.963	D	0.719	prob.delet.	N	0.433467687	None	None	N
L/R	0.9335	likely_pathogenic	0.8964	pathogenic	-2.054	Highly Destabilizing	0.896	D	0.725	prob.delet.	N	0.432774254	None	None	N
L/S	0.8567	likely_pathogenic	0.8081	pathogenic	-3.549	Highly Destabilizing	0.85	D	0.749	deleterious	None	None	None	None	N
L/T	0.5643	likely_pathogenic	0.5378	ambiguous	-3.176	Highly Destabilizing	0.617	D	0.71	prob.delet.	None	None	None	None	N
L/V	0.0857	likely_benign	0.0887	benign	-1.816	Destabilizing	0.002	N	0.404	neutral	N	0.438102716	None	None	N
L/W	0.7342	likely_pathogenic	0.5963	pathogenic	-2.237	Highly Destabilizing	0.992	D	0.705	prob.neutral	None	None	None	None	N
L/Y	0.7726	likely_pathogenic	0.6345	pathogenic	-2.004	Highly Destabilizing	0.739	D	0.732	prob.delet.	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.