TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23893	71902;71903;71904	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
N2AB	22252	66979;66980;66981	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
N2A	21325	64198;64199;64200	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
N2B	14828	44707;44708;44709	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
Novex-1	14953	45082;45083;45084	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
Novex-2	15020	45283;45284;45285	chr2:178574455;178574454;178574453	chr2:179439182;179439181;179439180
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: Fn3-61
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.6503
• 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/E	rs777818650	None	0.067	N	0.225	0.118	0.112648838833	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs777818650	None	0.067	N	0.225	0.118	0.112648838833	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
D/E	rs777818650	None	0.067	N	0.225	0.118	0.112648838833	gnomAD-4.0.0	1.05362E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35632E-05	0	1.60123E-05
D/N	rs753690633	-0.029	0.988	N	0.732	0.363	0.240491677333	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
D/N	rs753690633	-0.029	0.988	N	0.732	0.363	0.240491677333	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
D/N	rs753690633	-0.029	0.988	N	0.732	0.363	0.240491677333	gnomAD-4.0.0	1.54942E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.11929E-05	0	0
D/V	rs1449843654	0.092	0.994	N	0.686	0.507	0.544037764837	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/V	rs1449843654	0.092	0.994	N	0.686	0.507	0.544037764837	gnomAD-4.0.0	8.21141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07948E-05	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	0.1949	likely_benign	0.1982	benign	-0.62	Destabilizing	0.958	D	0.627	neutral	N	0.433956051	None	None	N
D/C	0.7329	likely_pathogenic	0.7131	pathogenic	-0.06	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/E	0.2003	likely_benign	0.1983	benign	-0.587	Destabilizing	0.067	N	0.225	neutral	N	0.303298365	None	None	N
D/F	0.8106	likely_pathogenic	0.7774	pathogenic	-0.598	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
D/G	0.291	likely_benign	0.2809	benign	-0.848	Destabilizing	0.958	D	0.65	neutral	N	0.476421535	None	None	N
D/H	0.46	ambiguous	0.4207	ambiguous	-0.67	Destabilizing	0.998	D	0.652	neutral	N	0.48234743	None	None	N
D/I	0.5843	likely_pathogenic	0.56	ambiguous	-0.052	Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
D/K	0.5918	likely_pathogenic	0.5613	ambiguous	-0.015	Destabilizing	0.982	D	0.661	neutral	None	None	None	None	N
D/L	0.6146	likely_pathogenic	0.5954	pathogenic	-0.052	Destabilizing	0.991	D	0.675	prob.neutral	None	None	None	None	N
D/M	0.7746	likely_pathogenic	0.7629	pathogenic	0.323	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
D/N	0.1515	likely_benign	0.1441	benign	-0.307	Destabilizing	0.988	D	0.732	prob.delet.	N	0.423376485	None	None	N
D/P	0.5898	likely_pathogenic	0.6027	pathogenic	-0.219	Destabilizing	0.995	D	0.66	neutral	None	None	None	None	N
D/Q	0.4847	ambiguous	0.4861	ambiguous	-0.29	Destabilizing	0.982	D	0.725	prob.delet.	None	None	None	None	N
D/R	0.6224	likely_pathogenic	0.5762	pathogenic	0.103	Stabilizing	0.991	D	0.647	neutral	None	None	None	None	N
D/S	0.1609	likely_benign	0.1646	benign	-0.445	Destabilizing	0.968	D	0.683	prob.neutral	None	None	None	None	N
D/T	0.3605	ambiguous	0.3642	ambiguous	-0.271	Destabilizing	0.991	D	0.668	neutral	None	None	None	None	N
D/V	0.3607	ambiguous	0.3366	benign	-0.219	Destabilizing	0.994	D	0.686	prob.neutral	N	0.460356005	None	None	N
D/W	0.9465	likely_pathogenic	0.9308	pathogenic	-0.44	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
D/Y	0.3989	ambiguous	0.3542	ambiguous	-0.365	Destabilizing	0.999	D	0.689	prob.neutral	N	0.490158837	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.