TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14477	43654;43655;43656	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
N2AB	12836	38731;38732;38733	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
N2A	11909	35950;35951;35952	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
N2B	5412	16459;16460;16461	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
Novex-1	5537	16834;16835;16836	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
Novex-2	5604	17035;17036;17037	chr2:178632577;178632576;178632575	chr2:179497304;179497303;179497302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-95
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.0835
• 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
Y/H	None	None	1.0	D	0.794	0.864	0.857532584068	gnomAD-4.0.0	3.18445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85986E-06	1.43336E-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
Y/A	0.9934	likely_pathogenic	0.9905	pathogenic	-2.475	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/C	0.9091	likely_pathogenic	0.8804	pathogenic	-1.444	Destabilizing	1.0	D	0.881	deleterious	D	0.710925543	None	None	N
Y/D	0.9951	likely_pathogenic	0.9942	pathogenic	-3.236	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.710925543	None	None	N
Y/E	0.9978	likely_pathogenic	0.9976	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/F	0.2631	likely_benign	0.2209	benign	-0.848	Destabilizing	0.999	D	0.687	prob.neutral	D	0.629889139	None	None	N
Y/G	0.9832	likely_pathogenic	0.9823	pathogenic	-2.922	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.9742	likely_pathogenic	0.971	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.794	deleterious	D	0.711318442	None	None	N
Y/I	0.8868	likely_pathogenic	0.8081	pathogenic	-0.986	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.9977	pathogenic	-1.97	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/L	0.8262	likely_pathogenic	0.769	pathogenic	-0.986	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
Y/M	0.9666	likely_pathogenic	0.9467	pathogenic	-0.884	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9705	likely_pathogenic	0.9708	pathogenic	-2.935	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.710925543	None	None	N
Y/P	0.9977	likely_pathogenic	0.9975	pathogenic	-1.499	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.9975	pathogenic	-2.518	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9938	likely_pathogenic	0.993	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/S	0.9881	likely_pathogenic	0.986	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.710925543	None	None	N
Y/T	0.9931	likely_pathogenic	0.9902	pathogenic	-2.808	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/V	0.8544	likely_pathogenic	0.7738	pathogenic	-1.499	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/W	0.85	likely_pathogenic	0.8378	pathogenic	-0.198	Destabilizing	1.0	D	0.783	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.