TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3132	9619;9620;9621	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
N2AB	3132	9619;9620;9621	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
N2A	3132	9619;9620;9621	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
N2B	3086	9481;9482;9483	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
Novex-1	3086	9481;9482;9483	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
Novex-2	3086	9481;9482;9483	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561
Novex-3	3132	9619;9620;9621	chr2:178767836;178767835;178767834	chr2:179632563;179632562;179632561

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-21
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.5598
• 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	rs1293502713	None	1.0	N	0.815	0.537	0.301789629655	gnomAD-4.0.0	1.59052E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.4108E-04	0	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	0.3503	ambiguous	0.4237	ambiguous	-0.272	Destabilizing	1.0	D	0.668	neutral	N	0.429050617	None	None	I
G/C	0.6733	likely_pathogenic	0.7464	pathogenic	-1.032	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
G/D	0.8724	likely_pathogenic	0.9009	pathogenic	-0.404	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/E	0.8994	likely_pathogenic	0.922	pathogenic	-0.541	Destabilizing	1.0	D	0.815	deleterious	N	0.348360382	None	None	I
G/F	0.9559	likely_pathogenic	0.973	pathogenic	-0.917	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
G/H	0.9336	likely_pathogenic	0.9547	pathogenic	-0.3	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/I	0.948	likely_pathogenic	0.9675	pathogenic	-0.436	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
G/K	0.9524	likely_pathogenic	0.962	pathogenic	-0.694	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/L	0.8878	likely_pathogenic	0.9276	pathogenic	-0.436	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/M	0.9226	likely_pathogenic	0.9524	pathogenic	-0.71	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
G/N	0.8324	likely_pathogenic	0.8869	pathogenic	-0.453	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/P	0.9914	likely_pathogenic	0.9926	pathogenic	-0.354	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/Q	0.877	likely_pathogenic	0.906	pathogenic	-0.663	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/R	0.8642	likely_pathogenic	0.8886	pathogenic	-0.308	Destabilizing	1.0	D	0.792	deleterious	N	0.386252899	None	None	I
G/S	0.3335	likely_benign	0.4273	ambiguous	-0.642	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/T	0.8218	likely_pathogenic	0.8847	pathogenic	-0.699	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/V	0.8686	likely_pathogenic	0.9137	pathogenic	-0.354	Destabilizing	1.0	D	0.778	deleterious	N	0.44501285	None	None	I
G/W	0.933	likely_pathogenic	0.9529	pathogenic	-1.036	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
G/Y	0.9395	likely_pathogenic	0.9595	pathogenic	-0.718	Destabilizing	1.0	D	0.735	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.