TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5804	17635;17636;17637	chr2:178731356;178731355;178731354	chr2:179596083;179596082;179596081
N2AB	5487	16684;16685;16686	chr2:178731356;178731355;178731354	chr2:179596083;179596082;179596081
N2A	4560	13903;13904;13905	chr2:178731356;178731355;178731354	chr2:179596083;179596082;179596081
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-41
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0874
• 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
A/S	rs773397477	-2.109	0.999	D	0.577	0.581	0.600586691565	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
A/S	rs773397477	-2.109	0.999	D	0.577	0.581	0.600586691565	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85837E-06	0	0
A/T	None	None	0.999	D	0.701	0.63	0.635264866943	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85837E-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
A/C	0.8498	likely_pathogenic	0.8421	pathogenic	-1.498	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/D	0.9966	likely_pathogenic	0.9966	pathogenic	-2.679	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.606729735	None	None	N
A/E	0.9883	likely_pathogenic	0.9891	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/F	0.9121	likely_pathogenic	0.9141	pathogenic	-0.819	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
A/G	0.4343	ambiguous	0.4406	ambiguous	-1.95	Destabilizing	0.999	D	0.571	neutral	D	0.606326127	None	None	N
A/H	0.9965	likely_pathogenic	0.9966	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
A/I	0.4924	ambiguous	0.5061	ambiguous	-0.147	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
A/K	0.9978	likely_pathogenic	0.9978	pathogenic	-1.382	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/L	0.5439	ambiguous	0.572	pathogenic	-0.147	Destabilizing	0.504	D	0.481	neutral	None	None	None	None	N
A/M	0.7438	likely_pathogenic	0.7716	pathogenic	-0.545	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/N	0.9889	likely_pathogenic	0.9896	pathogenic	-1.767	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/P	0.9914	likely_pathogenic	0.9904	pathogenic	-0.547	Destabilizing	1.0	D	0.863	deleterious	D	0.606527931	None	None	N
A/Q	0.9852	likely_pathogenic	0.9862	pathogenic	-1.538	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/R	0.9925	likely_pathogenic	0.9923	pathogenic	-1.47	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
A/S	0.5273	ambiguous	0.5417	ambiguous	-2.185	Highly Destabilizing	0.999	D	0.577	neutral	D	0.606124322	None	None	N
A/T	0.5936	likely_pathogenic	0.6204	pathogenic	-1.838	Destabilizing	0.999	D	0.701	prob.neutral	D	0.605922518	None	None	N
A/V	0.2567	likely_benign	0.2688	benign	-0.547	Destabilizing	0.992	D	0.539	neutral	D	0.536529498	None	None	N
A/W	0.9957	likely_pathogenic	0.9958	pathogenic	-1.542	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/Y	0.9824	likely_pathogenic	0.9812	pathogenic	-1.065	Destabilizing	1.0	D	0.892	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.