TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17765	53518;53519;53520	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
N2AB	16124	48595;48596;48597	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
N2A	15197	45814;45815;45816	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
N2B	8700	26323;26324;26325	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
Novex-1	8825	26698;26699;26700	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
Novex-2	8892	26899;26900;26901	chr2:178607309;178607308;178607307	chr2:179472036;179472035;179472034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-17
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2544
• 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
P/S	rs1298494593	-0.616	1.0	D	0.891	0.708	0.745525825506	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
P/S	rs1298494593	-0.616	1.0	D	0.891	0.708	0.745525825506	gnomAD-4.0.0	1.59458E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86241E-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	0.9591	likely_pathogenic	0.9062	pathogenic	-1.596	Destabilizing	0.999	D	0.839	deleterious	D	0.598464633	None	None	I
P/C	0.9959	likely_pathogenic	0.9914	pathogenic	-1.845	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/D	0.9997	likely_pathogenic	0.9993	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
P/E	0.9993	likely_pathogenic	0.9981	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
P/F	0.9999	likely_pathogenic	0.9996	pathogenic	-1.149	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	I
P/G	0.9972	likely_pathogenic	0.9951	pathogenic	-1.916	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
P/H	0.9994	likely_pathogenic	0.998	pathogenic	-1.365	Destabilizing	1.0	D	0.9	deleterious	D	0.636448555	None	None	I
P/I	0.9981	likely_pathogenic	0.9938	pathogenic	-0.774	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
P/K	0.9996	likely_pathogenic	0.999	pathogenic	-1.443	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/L	0.9911	likely_pathogenic	0.9749	pathogenic	-0.774	Destabilizing	1.0	D	0.894	deleterious	D	0.62022739	None	None	I
P/M	0.999	likely_pathogenic	0.9974	pathogenic	-0.997	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/N	0.9998	likely_pathogenic	0.9993	pathogenic	-1.693	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	I
P/Q	0.9992	likely_pathogenic	0.9975	pathogenic	-1.862	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
P/R	0.9985	likely_pathogenic	0.9951	pathogenic	-0.975	Destabilizing	1.0	D	0.912	deleterious	D	0.636246751	None	None	I
P/S	0.9965	likely_pathogenic	0.9904	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.636044947	None	None	I
P/T	0.9949	likely_pathogenic	0.9857	pathogenic	-1.867	Destabilizing	1.0	D	0.888	deleterious	D	0.62022739	None	None	I
P/V	0.9926	likely_pathogenic	0.9806	pathogenic	-1.02	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.468	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
P/Y	0.9999	likely_pathogenic	0.9996	pathogenic	-1.136	Destabilizing	1.0	D	0.917	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.