TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1526	4801;4802;4803	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
N2AB	1526	4801;4802;4803	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
N2A	1526	4801;4802;4803	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
N2B	1480	4663;4664;4665	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
Novex-1	1480	4663;4664;4665	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
Novex-2	1480	4663;4664;4665	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214
Novex-3	1526	4801;4802;4803	chr2:178777489;178777488;178777487	chr2:179642216;179642215;179642214

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-6
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.2004
• 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
G/E	None	None	1.0	D	0.801	0.838	0.863051463707	gnomAD-4.0.0	1.32035E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.44375E-05	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
G/A	0.4908	ambiguous	0.5331	ambiguous	-0.797	Destabilizing	1.0	D	0.742	deleterious	D	0.667707306	None	None	I
G/C	0.8572	likely_pathogenic	0.8877	pathogenic	-0.995	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/D	0.8995	likely_pathogenic	0.9189	pathogenic	-1.545	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/E	0.9324	likely_pathogenic	0.9463	pathogenic	-1.521	Destabilizing	1.0	D	0.801	deleterious	D	0.83054444	None	None	I
G/F	0.9901	likely_pathogenic	0.9915	pathogenic	-1.025	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/H	0.9626	likely_pathogenic	0.9711	pathogenic	-1.627	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
G/I	0.9861	likely_pathogenic	0.9886	pathogenic	-0.123	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
G/K	0.9345	likely_pathogenic	0.945	pathogenic	-1.19	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/L	0.9743	likely_pathogenic	0.9784	pathogenic	-0.123	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
G/M	0.9833	likely_pathogenic	0.9868	pathogenic	-0.106	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/N	0.9219	likely_pathogenic	0.9372	pathogenic	-1.049	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/P	0.9976	likely_pathogenic	0.998	pathogenic	-0.304	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/Q	0.9201	likely_pathogenic	0.9372	pathogenic	-1.116	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/R	0.8475	likely_pathogenic	0.874	pathogenic	-1.037	Destabilizing	1.0	D	0.801	deleterious	D	0.829527062	None	None	I
G/S	0.4324	ambiguous	0.4821	ambiguous	-1.374	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/T	0.891	likely_pathogenic	0.9093	pathogenic	-1.253	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/V	0.9558	likely_pathogenic	0.9636	pathogenic	-0.304	Destabilizing	1.0	D	0.77	deleterious	D	0.829527062	None	None	I
G/W	0.9798	likely_pathogenic	0.9845	pathogenic	-1.558	Destabilizing	1.0	D	0.752	deleterious	D	0.829221243	None	None	I
G/Y	0.9858	likely_pathogenic	0.9886	pathogenic	-1.059	Destabilizing	1.0	D	0.751	deleterious	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.