TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25030	75313;75314;75315	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
N2AB	23389	70390;70391;70392	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
N2A	22462	67609;67610;67611	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
N2B	15965	48118;48119;48120	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
Novex-1	16090	48493;48494;48495	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
Novex-2	16157	48694;48695;48696	chr2:178571044;178571043;178571042	chr2:179435771;179435770;179435769
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-70
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1539
• 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/L	None	None	1.0	D	0.895	0.762	0.919050959195	gnomAD-4.0.0	6.84819E-07	None	None	None	None	N	None	2.99133E-05	0	None	0	0	None	0	0	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
P/A	0.8774	likely_pathogenic	0.8485	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.603254394	None	None	N
P/C	0.9927	likely_pathogenic	0.9896	pathogenic	-1.368	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/D	0.9984	likely_pathogenic	0.9983	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/E	0.9967	likely_pathogenic	0.9961	pathogenic	-2.682	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9993	pathogenic	-1.516	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/G	0.9875	likely_pathogenic	0.9851	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/H	0.9964	likely_pathogenic	0.9956	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.659377519	None	None	N
P/I	0.9948	likely_pathogenic	0.9921	pathogenic	-0.977	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/K	0.9986	likely_pathogenic	0.9983	pathogenic	-1.822	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/L	0.9757	likely_pathogenic	0.9658	pathogenic	-0.977	Destabilizing	1.0	D	0.895	deleterious	D	0.659175715	None	None	N
P/M	0.9952	likely_pathogenic	0.9932	pathogenic	-0.656	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/N	0.9972	likely_pathogenic	0.9967	pathogenic	-1.755	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/Q	0.995	likely_pathogenic	0.9937	pathogenic	-1.858	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/R	0.9956	likely_pathogenic	0.9947	pathogenic	-1.328	Destabilizing	1.0	D	0.893	deleterious	D	0.599943368	None	None	N
P/S	0.977	likely_pathogenic	0.9721	pathogenic	-2.182	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.571740722	None	None	N
P/T	0.9777	likely_pathogenic	0.9707	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.608099491	None	None	N
P/V	0.9815	likely_pathogenic	0.9744	pathogenic	-1.289	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.927	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9992	pathogenic	-1.642	Destabilizing	1.0	D	0.891	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.