TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22180	66763;66764;66765	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
N2AB	20539	61840;61841;61842	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
N2A	19612	59059;59060;59061	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
N2B	13115	39568;39569;39570	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
Novex-1	13240	39943;39944;39945	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
Novex-2	13307	40144;40145;40146	chr2:178581730;178581729;178581728	chr2:179446457;179446456;179446455
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-49
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.169
• 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
P/T	None	None	1.0	D	0.851	0.746	0.635145041397	gnomAD-4.0.0	1.60199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87429E-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
P/A	0.9021	likely_pathogenic	0.9297	pathogenic	-1.834	Destabilizing	1.0	D	0.836	deleterious	D	0.57973971	None	None	N
P/C	0.993	likely_pathogenic	0.9955	pathogenic	-1.156	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/D	0.9989	likely_pathogenic	0.9994	pathogenic	-1.909	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9985	pathogenic	-1.876	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9998	pathogenic	-1.385	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/G	0.9915	likely_pathogenic	0.9948	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/H	0.9976	likely_pathogenic	0.9986	pathogenic	-1.834	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/I	0.9957	likely_pathogenic	0.9967	pathogenic	-0.888	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9993	pathogenic	-1.637	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/L	0.9835	likely_pathogenic	0.9882	pathogenic	-0.888	Destabilizing	1.0	D	0.909	deleterious	D	0.615321622	None	None	N
P/M	0.9967	likely_pathogenic	0.998	pathogenic	-0.586	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/N	0.9987	likely_pathogenic	0.9992	pathogenic	-1.423	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Q	0.9973	likely_pathogenic	0.9984	pathogenic	-1.555	Destabilizing	1.0	D	0.844	deleterious	D	0.616330643	None	None	N
P/R	0.9961	likely_pathogenic	0.9977	pathogenic	-1.115	Destabilizing	1.0	D	0.902	deleterious	D	0.597323502	None	None	N
P/S	0.9901	likely_pathogenic	0.9935	pathogenic	-1.938	Destabilizing	1.0	D	0.856	deleterious	D	0.558209118	None	None	N
P/T	0.9832	likely_pathogenic	0.989	pathogenic	-1.794	Destabilizing	1.0	D	0.851	deleterious	D	0.615927035	None	None	N
P/V	0.9817	likely_pathogenic	0.9859	pathogenic	-1.17	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9999	pathogenic	-1.654	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9998	pathogenic	-1.382	Destabilizing	1.0	D	0.91	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.