TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29820	89683;89684;89685	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
N2AB	28179	84760;84761;84762	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
N2A	27252	81979;81980;81981	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
N2B	20755	62488;62489;62490	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
Novex-1	20880	62863;62864;62865	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
Novex-2	20947	63064;63065;63066	chr2:178553547;178553546;178553545	chr2:179418274;179418273;179418272
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: Fn3-105
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6604
• 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
E/K	rs1700193837	None	0.984	N	0.535	0.299	0.417334834585	gnomAD-4.0.0	2.0528E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69858E-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	0.1743	likely_benign	0.1661	benign	-0.298	Destabilizing	0.992	D	0.603	neutral	N	0.516537362	None	None	I
E/C	0.7936	likely_pathogenic	0.7903	pathogenic	-0.003	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
E/D	0.1053	likely_benign	0.1031	benign	-0.316	Destabilizing	0.996	D	0.535	neutral	N	0.476557608	None	None	I
E/F	0.6717	likely_pathogenic	0.6655	pathogenic	-0.254	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/G	0.2226	likely_benign	0.2059	benign	-0.46	Destabilizing	0.999	D	0.64	neutral	N	0.472672231	None	None	I
E/H	0.4453	ambiguous	0.4559	ambiguous	0.084	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	I
E/I	0.2653	likely_benign	0.2694	benign	0.083	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
E/K	0.1232	likely_benign	0.1261	benign	0.471	Stabilizing	0.984	D	0.535	neutral	N	0.508360596	None	None	I
E/L	0.3019	likely_benign	0.3065	benign	0.083	Stabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	I
E/M	0.3704	ambiguous	0.3725	ambiguous	0.128	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/N	0.2162	likely_benign	0.2186	benign	0.144	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
E/P	0.3929	ambiguous	0.4043	ambiguous	-0.025	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
E/Q	0.1342	likely_benign	0.1353	benign	0.163	Stabilizing	0.992	D	0.659	neutral	N	0.510246108	None	None	I
E/R	0.246	likely_benign	0.2471	benign	0.64	Stabilizing	0.538	D	0.341	neutral	None	None	None	None	I
E/S	0.1994	likely_benign	0.1983	benign	0.013	Stabilizing	0.997	D	0.648	neutral	None	None	None	None	I
E/T	0.2139	likely_benign	0.2187	benign	0.151	Stabilizing	0.999	D	0.662	neutral	None	None	None	None	I
E/V	0.1852	likely_benign	0.1803	benign	-0.025	Destabilizing	0.999	D	0.711	prob.delet.	N	0.471737633	None	None	I
E/W	0.8821	likely_pathogenic	0.8826	pathogenic	-0.129	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/Y	0.5388	ambiguous	0.5471	ambiguous	-0.011	Destabilizing	1.0	D	0.725	prob.delet.	None	None	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.