TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17969	54130;54131;54132	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
N2AB	16328	49207;49208;49209	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
N2A	15401	46426;46427;46428	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
N2B	8904	26935;26936;26937	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
Novex-1	9029	27310;27311;27312	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
Novex-2	9096	27511;27512;27513	chr2:178605272;178605271;178605270	chr2:179469999;179469998;179469997
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-114
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.491
• Predicted PPI site: I

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	rs780364455	-0.436	0.998	N	0.601	0.551	0.73779808135	gnomAD-2.1.1	4.34E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.69E-05	None	0	0	0
L/P	rs780364455	-0.436	0.998	N	0.601	0.551	0.73779808135	gnomAD-4.0.0	1.64259E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4993E-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
L/A	0.6595	likely_pathogenic	0.5247	ambiguous	-0.787	Destabilizing	0.97	D	0.528	neutral	None	None	None	None	I
L/C	0.8211	likely_pathogenic	0.7723	pathogenic	-0.938	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	I
L/D	0.9324	likely_pathogenic	0.885	pathogenic	0.156	Stabilizing	0.996	D	0.601	neutral	None	None	None	None	I
L/E	0.7771	likely_pathogenic	0.6706	pathogenic	0.131	Stabilizing	0.97	D	0.522	neutral	None	None	None	None	I
L/F	0.307	likely_benign	0.2591	benign	-0.498	Destabilizing	0.996	D	0.58	neutral	None	None	None	None	I
L/G	0.8336	likely_pathogenic	0.7395	pathogenic	-1.016	Destabilizing	0.996	D	0.551	neutral	None	None	None	None	I
L/H	0.6811	likely_pathogenic	0.5644	pathogenic	-0.266	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
L/I	0.1854	likely_benign	0.1609	benign	-0.274	Destabilizing	0.304	N	0.185	neutral	None	None	None	None	I
L/K	0.6262	likely_pathogenic	0.5477	ambiguous	-0.51	Destabilizing	0.304	N	0.282	neutral	None	None	None	None	I
L/M	0.1884	likely_benign	0.1654	benign	-0.55	Destabilizing	0.994	D	0.576	neutral	N	0.445781702	None	None	I
L/N	0.7677	likely_pathogenic	0.6466	pathogenic	-0.435	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	I
L/P	0.6139	likely_pathogenic	0.4616	ambiguous	-0.413	Destabilizing	0.998	D	0.601	neutral	N	0.464636822	None	None	I
L/Q	0.5443	ambiguous	0.4122	ambiguous	-0.51	Destabilizing	0.989	D	0.594	neutral	N	0.464463464	None	None	I
L/R	0.6016	likely_pathogenic	0.5183	ambiguous	-0.118	Destabilizing	0.977	D	0.511	neutral	N	0.464463464	None	None	I
L/S	0.7943	likely_pathogenic	0.652	pathogenic	-1.007	Destabilizing	0.97	D	0.494	neutral	None	None	None	None	I
L/T	0.5893	likely_pathogenic	0.4626	ambiguous	-0.906	Destabilizing	0.985	D	0.543	neutral	None	None	None	None	I
L/V	0.187	likely_benign	0.1537	benign	-0.413	Destabilizing	0.835	D	0.473	neutral	N	0.424422208	None	None	I
L/W	0.6399	likely_pathogenic	0.5782	pathogenic	-0.538	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	I
L/Y	0.6754	likely_pathogenic	0.5948	pathogenic	-0.302	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	I

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.