TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15824	47695;47696;47697	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
N2AB	14183	42772;42773;42774	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
N2A	13256	39991;39992;39993	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
N2B	6759	20500;20501;20502	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
Novex-1	6884	20875;20876;20877	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
Novex-2	6951	21076;21077;21078	chr2:178617881;178617880;178617879	chr2:179482608;179482607;179482606
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: Fn3-2
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4152
• 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	0.948	N	0.384	0.273	0.513280433867	gnomAD-4.0.0	4.78054E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.726E-06	1.43349E-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
V/A	0.1875	likely_benign	0.2186	benign	-0.789	Destabilizing	0.948	D	0.384	neutral	N	0.476952799	None	None	N
V/C	0.7953	likely_pathogenic	0.7793	pathogenic	-0.878	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
V/D	0.4181	ambiguous	0.4883	ambiguous	-0.426	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
V/E	0.3002	likely_benign	0.3454	ambiguous	-0.476	Destabilizing	0.999	D	0.683	prob.neutral	N	0.473056849	None	None	N
V/F	0.2147	likely_benign	0.2473	benign	-0.678	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	N
V/G	0.2604	likely_benign	0.3075	benign	-0.993	Destabilizing	0.999	D	0.733	prob.delet.	D	0.57888184	None	None	N
V/H	0.5936	likely_pathogenic	0.6109	pathogenic	-0.271	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/I	0.085	likely_benign	0.0886	benign	-0.37	Destabilizing	0.198	N	0.159	neutral	N	0.425133077	None	None	N
V/K	0.3168	likely_benign	0.3377	benign	-0.692	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
V/L	0.2043	likely_benign	0.2244	benign	-0.37	Destabilizing	0.9	D	0.333	neutral	N	0.467041343	None	None	N
V/M	0.1616	likely_benign	0.1838	benign	-0.563	Destabilizing	0.998	D	0.508	neutral	None	None	None	None	N
V/N	0.3054	likely_benign	0.3526	ambiguous	-0.595	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
V/P	0.6195	likely_pathogenic	0.6798	pathogenic	-0.475	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
V/Q	0.3043	likely_benign	0.3318	benign	-0.76	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
V/R	0.2864	likely_benign	0.3018	benign	-0.149	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/S	0.2343	likely_benign	0.2624	benign	-1.041	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
V/T	0.1641	likely_benign	0.1764	benign	-0.977	Destabilizing	0.992	D	0.421	neutral	None	None	None	None	N
V/W	0.8216	likely_pathogenic	0.8329	pathogenic	-0.763	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/Y	0.6322	likely_pathogenic	0.6351	pathogenic	-0.484	Destabilizing	0.999	D	0.574	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.