TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16420	49483;49484;49485	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
N2AB	14779	44560;44561;44562	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
N2A	13852	41779;41780;41781	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
N2B	7355	22288;22289;22290	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
Novex-1	7480	22663;22664;22665	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
Novex-2	7547	22864;22865;22866	chr2:178614139;178614138;178614137	chr2:179478866;179478865;179478864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-6
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.389
• 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
E/D	rs2056859473	None	0.999	N	0.472	0.289	0.229264304666	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
E/D	rs2056859473	None	0.999	N	0.472	0.289	0.229264304666	gnomAD-4.0.0	6.58857E-06	None	None	None	None	N	None	0	6.57117E-05	None	0	0	None	0	0	0	0	0
E/G	rs1402412207	-1.606	1.0	D	0.763	0.474	0.518585293439	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/G	rs1402412207	-1.606	1.0	D	0.763	0.474	0.518585293439	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	5.67408E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs764682084	-0.537	0.999	N	0.613	0.403	0.447609009685	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	3.57E-05	0
E/K	rs764682084	-0.537	0.999	N	0.613	0.403	0.447609009685	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs764682084	-0.537	0.999	N	0.613	0.403	0.447609009685	gnomAD-4.0.0	6.20235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.63203E-06	1.09835E-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
E/A	0.2533	likely_benign	0.2179	benign	-0.884	Destabilizing	0.999	D	0.709	prob.delet.	D	0.564289855	None	None	N
E/C	0.9252	likely_pathogenic	0.8971	pathogenic	-0.519	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.2803	likely_benign	0.2446	benign	-1.334	Destabilizing	0.999	D	0.472	neutral	N	0.467787014	None	None	N
E/F	0.9524	likely_pathogenic	0.9279	pathogenic	-0.3	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/G	0.4376	ambiguous	0.3569	ambiguous	-1.294	Destabilizing	1.0	D	0.763	deleterious	D	0.580346342	None	None	N
E/H	0.7982	likely_pathogenic	0.7309	pathogenic	-0.689	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/I	0.5445	ambiguous	0.4572	ambiguous	0.247	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/K	0.3713	ambiguous	0.2894	benign	-0.838	Destabilizing	0.999	D	0.613	neutral	N	0.508093089	None	None	N
E/L	0.6898	likely_pathogenic	0.5991	pathogenic	0.247	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/M	0.6415	likely_pathogenic	0.5642	pathogenic	0.797	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/N	0.4675	ambiguous	0.399	ambiguous	-1.329	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/P	0.6838	likely_pathogenic	0.6058	pathogenic	-0.108	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.1965	likely_benign	0.1674	benign	-1.143	Destabilizing	1.0	D	0.628	neutral	N	0.471927637	None	None	N
E/R	0.5717	likely_pathogenic	0.4803	ambiguous	-0.601	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.3503	ambiguous	0.3017	benign	-1.709	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.2862	likely_benign	0.2365	benign	-1.362	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/V	0.3337	likely_benign	0.2747	benign	-0.108	Destabilizing	1.0	D	0.796	deleterious	D	0.551105752	None	None	N
E/W	0.9851	likely_pathogenic	0.9746	pathogenic	-0.097	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.9024	likely_pathogenic	0.8599	pathogenic	-0.059	Destabilizing	1.0	D	0.776	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.