TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14029	42310;42311;42312	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
N2AB	12388	37387;37388;37389	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
N2A	11461	34606;34607;34608	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
N2B	4964	15115;15116;15117	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
Novex-1	5089	15490;15491;15492	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
Novex-2	5156	15691;15692;15693	chr2:178634789;178634788;178634787	chr2:179499516;179499515;179499514
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-90
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.8283
• 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
D/N	rs794729426	None	0.986	N	0.785	0.384	0.227934060464	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
D/N	rs794729426	None	0.986	N	0.785	0.384	0.227934060464	gnomAD-4.0.0	5.12963E-06	None	None	None	None	I	None	0	5.09286E-05	None	0	0	None	0	0	2.39521E-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
D/A	0.6521	likely_pathogenic	0.5898	pathogenic	-0.098	Destabilizing	0.986	D	0.635	neutral	N	0.493882557	None	None	I
D/C	0.9583	likely_pathogenic	0.9454	pathogenic	-0.125	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
D/E	0.2879	likely_benign	0.2566	benign	-0.254	Destabilizing	0.058	N	0.307	neutral	N	0.427664945	None	None	I
D/F	0.9432	likely_pathogenic	0.9235	pathogenic	-0.02	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
D/G	0.6562	likely_pathogenic	0.5934	pathogenic	-0.27	Destabilizing	0.952	D	0.733	deleterious	N	0.494724665	None	None	I
D/H	0.83	likely_pathogenic	0.7458	pathogenic	0.428	Stabilizing	0.998	D	0.757	deleterious	N	0.498190772	None	None	I
D/I	0.9006	likely_pathogenic	0.8613	pathogenic	0.299	Stabilizing	0.995	D	0.767	deleterious	None	None	None	None	I
D/K	0.938	likely_pathogenic	0.8901	pathogenic	0.364	Stabilizing	0.979	D	0.751	deleterious	None	None	None	None	I
D/L	0.8781	likely_pathogenic	0.8411	pathogenic	0.299	Stabilizing	0.989	D	0.665	prob.neutral	None	None	None	None	I
D/M	0.9566	likely_pathogenic	0.9397	pathogenic	0.173	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
D/N	0.4248	ambiguous	0.3453	ambiguous	0.037	Stabilizing	0.986	D	0.785	deleterious	N	0.494724665	None	None	I
D/P	0.9405	likely_pathogenic	0.9163	pathogenic	0.188	Stabilizing	0.995	D	0.7	prob.delet.	None	None	None	None	I
D/Q	0.8526	likely_pathogenic	0.7861	pathogenic	0.069	Stabilizing	0.979	D	0.725	deleterious	None	None	None	None	I
D/R	0.9437	likely_pathogenic	0.9025	pathogenic	0.642	Stabilizing	0.989	D	0.677	prob.neutral	None	None	None	None	I
D/S	0.4968	ambiguous	0.427	ambiguous	-0.069	Destabilizing	0.963	D	0.689	prob.delet.	None	None	None	None	I
D/T	0.7738	likely_pathogenic	0.7239	pathogenic	0.07	Stabilizing	0.989	D	0.738	deleterious	None	None	None	None	I
D/V	0.801	likely_pathogenic	0.7387	pathogenic	0.188	Stabilizing	0.993	D	0.663	prob.neutral	N	0.49840492	None	None	I
D/W	0.987	likely_pathogenic	0.9781	pathogenic	0.086	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
D/Y	0.7871	likely_pathogenic	0.7045	pathogenic	0.219	Stabilizing	0.999	D	0.746	deleterious	N	0.49840492	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.