TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2678	8257;8258;8259	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
N2AB	2678	8257;8258;8259	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
N2A	2678	8257;8258;8259	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
N2B	2632	8119;8120;8121	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
Novex-1	2632	8119;8120;8121	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
Novex-2	2632	8119;8120;8121	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020
Novex-3	2678	8257;8258;8259	chr2:178771295;178771294;178771293	chr2:179636022;179636021;179636020

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-16
• Domain position: 58
• Structural Position: 140
• Q(SASA): 0.1144
• 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
I/T	rs1312609443	None	0.961	D	0.785	0.779	0.840607677293	gnomAD-4.0.0	1.59059E-06	None	None	None	None	N	None	5.65163E-05	0	None	0	0	None	0	0	0	0	0
I/V	None	None	0.248	D	0.307	0.464	0.738248460819	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.7226	likely_pathogenic	0.7639	pathogenic	-2.947	Highly Destabilizing	0.97	D	0.724	prob.delet.	None	None	None	None	N
I/C	0.9076	likely_pathogenic	0.9265	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
I/D	0.9848	likely_pathogenic	0.9845	pathogenic	-3.582	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
I/E	0.9644	likely_pathogenic	0.9661	pathogenic	-3.325	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
I/F	0.2503	likely_benign	0.2744	benign	-1.798	Destabilizing	0.151	N	0.386	neutral	D	0.579273579	None	None	N
I/G	0.9601	likely_pathogenic	0.967	pathogenic	-3.521	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
I/H	0.9056	likely_pathogenic	0.9076	pathogenic	-2.971	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/K	0.8984	likely_pathogenic	0.8956	pathogenic	-2.4	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
I/L	0.1613	likely_benign	0.1851	benign	-1.257	Destabilizing	0.689	D	0.453	neutral	D	0.604315515	None	None	N
I/M	0.1795	likely_benign	0.197	benign	-1.351	Destabilizing	0.994	D	0.704	prob.neutral	D	0.671200466	None	None	N
I/N	0.869	likely_pathogenic	0.8756	pathogenic	-2.899	Highly Destabilizing	0.998	D	0.867	deleterious	D	0.778916848	None	None	N
I/P	0.9792	likely_pathogenic	0.9767	pathogenic	-1.806	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
I/Q	0.9143	likely_pathogenic	0.9153	pathogenic	-2.711	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
I/R	0.8412	likely_pathogenic	0.8356	pathogenic	-2.08	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
I/S	0.8011	likely_pathogenic	0.8212	pathogenic	-3.569	Highly Destabilizing	0.994	D	0.826	deleterious	D	0.778916848	None	None	N
I/T	0.6124	likely_pathogenic	0.6489	pathogenic	-3.162	Highly Destabilizing	0.961	D	0.785	deleterious	D	0.705989114	None	None	N
I/V	0.1216	likely_benign	0.1373	benign	-1.806	Destabilizing	0.248	N	0.307	neutral	D	0.618906114	None	None	N
I/W	0.9267	likely_pathogenic	0.9325	pathogenic	-2.24	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/Y	0.7893	likely_pathogenic	0.7975	pathogenic	-2.002	Highly Destabilizing	0.983	D	0.784	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.