TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7535	22828;22829;22830	chr2:178722060;178722059;178722058	chr2:179586787;179586786;179586785
N2AB	7218	21877;21878;21879	chr2:178722060;178722059;178722058	chr2:179586787;179586786;179586785
N2A	6291	19096;19097;19098	chr2:178722060;178722059;178722058	chr2:179586787;179586786;179586785
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-60
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3281
• 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/G	rs773956492	None	0.896	N	0.623	0.507	0.644471222209	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56251E-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	0.2246	likely_benign	0.2751	benign	-0.906	Destabilizing	0.896	D	0.532	neutral	N	0.49069644	None	None	I
E/C	0.9342	likely_pathogenic	0.9402	pathogenic	-0.62	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	I
E/D	0.3161	likely_benign	0.3955	ambiguous	-1.255	Destabilizing	0.896	D	0.479	neutral	N	0.514108424	None	None	I
E/F	0.8473	likely_pathogenic	0.8831	pathogenic	-0.393	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	I
E/G	0.4437	ambiguous	0.4902	ambiguous	-1.296	Destabilizing	0.896	D	0.623	neutral	N	0.514929988	None	None	I
E/H	0.5877	likely_pathogenic	0.67	pathogenic	-0.876	Destabilizing	0.988	D	0.549	neutral	None	None	None	None	I
E/I	0.4507	ambiguous	0.5107	ambiguous	0.17	Stabilizing	0.976	D	0.717	prob.delet.	None	None	None	None	I
E/K	0.2371	likely_benign	0.2701	benign	-1.202	Destabilizing	0.811	D	0.501	neutral	N	0.510990761	None	None	I
E/L	0.5497	ambiguous	0.6379	pathogenic	0.17	Stabilizing	0.919	D	0.637	neutral	None	None	None	None	I
E/M	0.5829	likely_pathogenic	0.6403	pathogenic	0.698	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/N	0.5093	ambiguous	0.5987	pathogenic	-1.506	Destabilizing	0.919	D	0.483	neutral	None	None	None	None	I
E/P	0.9317	likely_pathogenic	0.9671	pathogenic	-0.168	Destabilizing	0.988	D	0.649	neutral	None	None	None	None	I
E/Q	0.15	likely_benign	0.176	benign	-1.309	Destabilizing	0.211	N	0.408	neutral	D	0.527768368	None	None	I
E/R	0.3503	ambiguous	0.4076	ambiguous	-0.953	Destabilizing	0.261	N	0.391	neutral	None	None	None	None	I
E/S	0.2852	likely_benign	0.3495	ambiguous	-1.888	Destabilizing	0.851	D	0.441	neutral	None	None	None	None	I
E/T	0.2698	likely_benign	0.3331	benign	-1.575	Destabilizing	0.132	N	0.435	neutral	None	None	None	None	I
E/V	0.2788	likely_benign	0.33	benign	-0.168	Destabilizing	0.968	D	0.642	neutral	D	0.52528821	None	None	I
E/W	0.9573	likely_pathogenic	0.9647	pathogenic	-0.268	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
E/Y	0.7872	likely_pathogenic	0.8299	pathogenic	-0.221	Destabilizing	0.996	D	0.705	prob.neutral	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.