TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28600	86023;86024;86025	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
N2AB	26959	81100;81101;81102	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
N2A	26032	78319;78320;78321	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
N2B	19535	58828;58829;58830	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
Novex-1	19660	59203;59204;59205	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
Novex-2	19727	59404;59405;59406	chr2:178560334;178560333;178560332	chr2:179425061;179425060;179425059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-96
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2549
• 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
V/A	None	None	0.999	N	0.559	0.402	0.495970961353	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
V/A	0.4262	ambiguous	0.4121	ambiguous	-1.365	Destabilizing	0.999	D	0.559	neutral	N	0.448832289	None	None	N
V/C	0.7539	likely_pathogenic	0.7602	pathogenic	-0.973	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/D	0.9119	likely_pathogenic	0.918	pathogenic	-1.234	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/E	0.8305	likely_pathogenic	0.8438	pathogenic	-1.211	Destabilizing	1.0	D	0.788	deleterious	N	0.477863245	None	None	N
V/F	0.5109	ambiguous	0.5142	ambiguous	-0.965	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/G	0.5674	likely_pathogenic	0.5723	pathogenic	-1.702	Destabilizing	1.0	D	0.785	deleterious	N	0.483498785	None	None	N
V/H	0.9313	likely_pathogenic	0.9355	pathogenic	-1.225	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.0964	likely_benign	0.0927	benign	-0.538	Destabilizing	0.997	D	0.459	neutral	N	0.510360751	None	None	N
V/K	0.9214	likely_pathogenic	0.9317	pathogenic	-1.276	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
V/L	0.4206	ambiguous	0.4172	ambiguous	-0.538	Destabilizing	0.997	D	0.533	neutral	N	0.502202627	None	None	N
V/M	0.3421	ambiguous	0.3313	benign	-0.454	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
V/N	0.7631	likely_pathogenic	0.7509	pathogenic	-1.151	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/P	0.9534	likely_pathogenic	0.9546	pathogenic	-0.779	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/Q	0.8247	likely_pathogenic	0.8326	pathogenic	-1.263	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/R	0.8947	likely_pathogenic	0.908	pathogenic	-0.784	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/S	0.612	likely_pathogenic	0.5854	pathogenic	-1.661	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/T	0.5263	ambiguous	0.4927	ambiguous	-1.52	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
V/W	0.9678	likely_pathogenic	0.9714	pathogenic	-1.199	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/Y	0.8823	likely_pathogenic	0.89	pathogenic	-0.886	Destabilizing	1.0	D	0.817	deleterious	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.