TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14569	43930;43931;43932	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
N2AB	12928	39007;39008;39009	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
N2A	12001	36226;36227;36228	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
N2B	5504	16735;16736;16737	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
Novex-1	5629	17110;17111;17112	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
Novex-2	5696	17311;17312;17313	chr2:178632189;178632188;178632187	chr2:179496916;179496915;179496914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-96
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.3712
• 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	rs1262651823	None	0.999	D	0.553	0.323	0.29527378943	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
E/D	rs1262651823	None	0.999	D	0.553	0.323	0.29527378943	gnomAD-4.0.0	3.10798E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.24657E-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
E/A	0.3767	ambiguous	0.3689	ambiguous	-1.127	Destabilizing	0.999	D	0.719	prob.delet.	D	0.595050717	None	None	N
E/C	0.9637	likely_pathogenic	0.9626	pathogenic	-0.535	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/D	0.4216	ambiguous	0.3229	benign	-1.233	Destabilizing	0.999	D	0.553	neutral	D	0.597156617	None	None	N
E/F	0.9239	likely_pathogenic	0.9071	pathogenic	-0.515	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/G	0.5403	ambiguous	0.5299	ambiguous	-1.528	Destabilizing	1.0	D	0.796	deleterious	D	0.638780019	None	None	N
E/H	0.7694	likely_pathogenic	0.735	pathogenic	-0.724	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/I	0.5939	likely_pathogenic	0.5388	ambiguous	-0.013	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
E/K	0.3441	ambiguous	0.3107	benign	-0.593	Destabilizing	0.999	D	0.635	neutral	D	0.533604368	None	None	N
E/L	0.7313	likely_pathogenic	0.6928	pathogenic	-0.013	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
E/M	0.6788	likely_pathogenic	0.6533	pathogenic	0.557	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
E/N	0.6595	likely_pathogenic	0.5802	pathogenic	-1.158	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/P	0.9951	likely_pathogenic	0.9931	pathogenic	-0.364	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/Q	0.2827	likely_benign	0.2689	benign	-1.003	Destabilizing	1.0	D	0.691	prob.neutral	N	0.506495901	None	None	N
E/R	0.5497	ambiguous	0.5207	ambiguous	-0.367	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/S	0.4587	ambiguous	0.4314	ambiguous	-1.572	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
E/T	0.4456	ambiguous	0.4106	ambiguous	-1.213	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/V	0.362	ambiguous	0.3222	benign	-0.364	Destabilizing	1.0	D	0.845	deleterious	N	0.50419406	None	None	N
E/W	0.975	likely_pathogenic	0.9682	pathogenic	-0.204	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/Y	0.8965	likely_pathogenic	0.8672	pathogenic	-0.203	Destabilizing	1.0	D	0.871	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.