TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29046	87361;87362;87363	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
N2AB	27405	82438;82439;82440	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
N2A	26478	79657;79658;79659	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
N2B	19981	60166;60167;60168	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
Novex-1	20106	60541;60542;60543	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
Novex-2	20173	60742;60743;60744	chr2:178558218;178558217;178558216	chr2:179422945;179422944;179422943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-145
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3726
• 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
M/I	rs1559264784	None	0.985	N	0.401	0.352	0.601307451256	gnomAD-4.0.0	6.87441E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87864E-05	0	0	0	0
M/K	None	None	0.994	N	0.383	0.508	0.7005188687	gnomAD-4.0.0	1.37497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80129E-06	0	0
M/R	rs143975327	1.288	0.998	N	0.34	0.551	None	gnomAD-2.1.1	2.13861E-04	None	None	None	None	N	None	2.33723E-03	0	None	0	5.27E-05	None	0	None	0	0	1.43637E-04
M/R	rs143975327	1.288	0.998	N	0.34	0.551	None	gnomAD-3.1.2	6.56814E-04	None	None	None	None	N	None	2.24259E-03	4.57995E-04	0	0	0	None	0	0	0	0	0
M/R	rs143975327	1.288	0.998	N	0.34	0.551	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	2.3E-03	0	None	None	0	0	None	None	None	0	None
M/R	rs143975327	1.288	0.998	N	0.34	0.551	None	gnomAD-4.0.0	1.19481E-04	None	None	None	None	N	None	2.37425E-03	1.54852E-04	None	0	0	None	0	0	1.69728E-06	0	6.42797E-05
M/T	rs143975327	0.822	0.994	N	0.4	0.487	0.726377241608	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.11E-06	0
M/T	rs143975327	0.822	0.994	N	0.4	0.487	0.726377241608	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/T	rs143975327	0.822	0.994	N	0.4	0.487	0.726377241608	gnomAD-4.0.0	3.11172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.24316E-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
M/A	0.7612	likely_pathogenic	0.752	pathogenic	-2.785	Highly Destabilizing	0.989	D	0.411	neutral	None	None	None	None	N
M/C	0.8244	likely_pathogenic	0.8314	pathogenic	-1.526	Destabilizing	1.0	D	0.367	neutral	None	None	None	None	N
M/D	0.9608	likely_pathogenic	0.9553	pathogenic	-1.386	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
M/E	0.8595	likely_pathogenic	0.8521	pathogenic	-1.297	Destabilizing	0.999	D	0.407	neutral	None	None	None	None	N
M/F	0.4702	ambiguous	0.4381	ambiguous	-1.479	Destabilizing	0.999	D	0.319	neutral	None	None	None	None	N
M/G	0.8238	likely_pathogenic	0.805	pathogenic	-3.152	Highly Destabilizing	0.995	D	0.482	neutral	None	None	None	None	N
M/H	0.8876	likely_pathogenic	0.8801	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.481	neutral	None	None	None	None	N
M/I	0.5736	likely_pathogenic	0.6116	pathogenic	-1.767	Destabilizing	0.985	D	0.401	neutral	N	0.492185996	None	None	N
M/K	0.6097	likely_pathogenic	0.6051	pathogenic	-1.42	Destabilizing	0.994	D	0.383	neutral	N	0.494786371	None	None	N
M/L	0.1309	likely_benign	0.1216	benign	-1.767	Destabilizing	0.927	D	0.229	neutral	N	0.417282805	None	None	N
M/N	0.8686	likely_pathogenic	0.8637	pathogenic	-1.282	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
M/P	0.8687	likely_pathogenic	0.8506	pathogenic	-2.087	Highly Destabilizing	0.999	D	0.45	neutral	None	None	None	None	N
M/Q	0.6821	likely_pathogenic	0.6769	pathogenic	-1.286	Destabilizing	0.999	D	0.336	neutral	None	None	None	None	N
M/R	0.6187	likely_pathogenic	0.5949	pathogenic	-0.94	Destabilizing	0.998	D	0.34	neutral	N	0.494959729	None	None	N
M/S	0.8121	likely_pathogenic	0.8051	pathogenic	-1.922	Destabilizing	0.995	D	0.372	neutral	None	None	None	None	N
M/T	0.3993	ambiguous	0.3903	ambiguous	-1.724	Destabilizing	0.994	D	0.4	neutral	N	0.475237818	None	None	N
M/V	0.1624	likely_benign	0.1674	benign	-2.087	Highly Destabilizing	0.985	D	0.337	neutral	N	0.488372112	None	None	N
M/W	0.7796	likely_pathogenic	0.7647	pathogenic	-1.395	Destabilizing	1.0	D	0.407	neutral	None	None	None	None	N
M/Y	0.8222	likely_pathogenic	0.8081	pathogenic	-1.568	Destabilizing	0.999	D	0.343	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.