TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32965	99118;99119;99120	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
N2AB	31324	94195;94196;94197	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
N2A	30397	91414;91415;91416	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
N2B	23900	71923;71924;71925	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
Novex-1	24025	72298;72299;72300	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
Novex-2	24092	72499;72500;72501	chr2:178539042;178539041;178539040	chr2:179403769;179403768;179403767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-128
• Domain position: 70
• Structural Position: 100
• Q(SASA): 0.811
• 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
D/G	rs767147750	-0.216	1.0	N	0.748	0.5	0.266385636622	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/G	rs767147750	-0.216	1.0	N	0.748	0.5	0.266385636622	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85866E-06	0	0
D/H	rs186405108	0.004	1.0	N	0.745	0.386	None	gnomAD-2.1.1	2.10666E-04	None	None	None	None	N	None	4.13E-05	2.83E-05	None	0	0	None	0	None	1.99968E-04	3.9079E-04	2.80662E-04
D/H	rs186405108	0.004	1.0	N	0.745	0.386	None	gnomAD-3.1.2	2.03754E-04	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	4.11571E-04	0	4.78011E-04
D/H	rs186405108	0.004	1.0	N	0.745	0.386	None	gnomAD-4.0.0	3.56337E-04	None	None	None	None	N	None	8.01111E-05	3.33444E-05	None	0	0	None	1.71848E-04	0	4.5518E-04	0	3.04253E-04
D/N	rs186405108	0.003	1.0	N	0.761	0.368	None	gnomAD-2.1.1	5.71E-05	None	None	None	None	N	None	6.61157E-04	0	None	0	0	None	0	None	0	0	0
D/N	rs186405108	0.003	1.0	N	0.761	0.368	None	gnomAD-3.1.2	1.70891E-04	None	None	None	None	N	None	6.03427E-04	6.55E-05	0	0	0	None	0	0	0	0	0
D/N	rs186405108	0.003	1.0	N	0.761	0.368	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
D/N	rs186405108	0.003	1.0	N	0.761	0.368	None	gnomAD-4.0.0	3.34623E-05	None	None	None	None	N	None	6.53177E-04	1.66667E-05	None	0	0	None	0	0	2.54292E-06	0	1.60077E-05

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	0.3573	ambiguous	0.3734	ambiguous	-0.223	Destabilizing	1.0	D	0.773	deleterious	N	0.457817132	None	None	N
D/C	0.8474	likely_pathogenic	0.842	pathogenic	-0.05	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
D/E	0.2632	likely_benign	0.2797	benign	-0.264	Destabilizing	1.0	D	0.498	neutral	N	0.484753017	None	None	N
D/F	0.8051	likely_pathogenic	0.812	pathogenic	-0.188	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
D/G	0.1916	likely_benign	0.2029	benign	-0.417	Destabilizing	1.0	D	0.748	deleterious	N	0.37088322	None	None	N
D/H	0.5303	ambiguous	0.5476	ambiguous	0.019	Stabilizing	1.0	D	0.745	deleterious	N	0.490236195	None	None	N
D/I	0.8331	likely_pathogenic	0.8264	pathogenic	0.239	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/K	0.7024	likely_pathogenic	0.7228	pathogenic	0.16	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/L	0.6748	likely_pathogenic	0.6809	pathogenic	0.239	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/M	0.8404	likely_pathogenic	0.8442	pathogenic	0.284	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
D/N	0.1032	likely_benign	0.1074	benign	-0.021	Destabilizing	1.0	D	0.761	deleterious	N	0.432246684	None	None	N
D/P	0.9705	likely_pathogenic	0.9719	pathogenic	0.107	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
D/Q	0.6054	likely_pathogenic	0.6237	pathogenic	0.007	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/R	0.7462	likely_pathogenic	0.7658	pathogenic	0.384	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/S	0.2034	likely_benign	0.2136	benign	-0.172	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
D/T	0.5219	ambiguous	0.5332	ambiguous	-0.028	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/V	0.6424	likely_pathogenic	0.634	pathogenic	0.107	Stabilizing	1.0	D	0.809	deleterious	N	0.474864731	None	None	N
D/W	0.9693	likely_pathogenic	0.9709	pathogenic	-0.09	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/Y	0.4104	ambiguous	0.4211	ambiguous	0.034	Stabilizing	1.0	D	0.789	deleterious	N	0.46984228	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.