TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8703	26332;26333;26334	chr2:178715079;178715078;178715077	chr2:179579806;179579805;179579804
N2AB	8386	25381;25382;25383	chr2:178715079;178715078;178715077	chr2:179579806;179579805;179579804
N2A	7459	22600;22601;22602	chr2:178715079;178715078;178715077	chr2:179579806;179579805;179579804
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-72
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2149
• 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/P	None	None	1.0	N	0.735	0.551	0.871880940535	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85897E-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
L/A	0.3115	likely_benign	0.3953	ambiguous	-2.131	Highly Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
L/C	0.5806	likely_pathogenic	0.6367	pathogenic	-1.363	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
L/D	0.7817	likely_pathogenic	0.8607	pathogenic	-1.966	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/E	0.4591	ambiguous	0.5749	pathogenic	-1.936	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/F	0.1316	likely_benign	0.1664	benign	-1.537	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
L/G	0.5474	ambiguous	0.6422	pathogenic	-2.498	Highly Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
L/H	0.2379	likely_benign	0.3362	benign	-1.695	Destabilizing	0.867	D	0.497	neutral	None	None	None	None	N
L/I	0.1007	likely_benign	0.1091	benign	-1.161	Destabilizing	0.271	N	0.235	neutral	None	None	None	None	N
L/K	0.3418	ambiguous	0.4494	ambiguous	-1.512	Destabilizing	0.995	D	0.693	prob.neutral	None	None	None	None	N
L/M	0.1225	likely_benign	0.1279	benign	-0.858	Destabilizing	0.998	D	0.618	neutral	N	0.50497558	None	None	N
L/N	0.4004	ambiguous	0.5007	ambiguous	-1.378	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/P	0.5084	ambiguous	0.6583	pathogenic	-1.457	Destabilizing	1.0	D	0.735	prob.delet.	N	0.516319223	None	None	N
L/Q	0.1498	likely_benign	0.2126	benign	-1.57	Destabilizing	1.0	D	0.693	prob.neutral	N	0.515220358	None	None	N
L/R	0.2133	likely_benign	0.3133	benign	-0.867	Destabilizing	1.0	D	0.698	prob.neutral	N	0.495615877	None	None	N
L/S	0.2743	likely_benign	0.3869	ambiguous	-2.01	Highly Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
L/T	0.2506	likely_benign	0.3105	benign	-1.865	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
L/V	0.1132	likely_benign	0.1304	benign	-1.457	Destabilizing	0.851	D	0.485	neutral	D	0.524477346	None	None	N
L/W	0.2337	likely_benign	0.316	benign	-1.651	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
L/Y	0.3748	ambiguous	0.4487	ambiguous	-1.45	Destabilizing	0.994	D	0.687	prob.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.