TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5392	16399;16400;16401	chr2:178733002;178733001;178733000	chr2:179597729;179597728;179597727
N2AB	5075	15448;15449;15450	chr2:178733002;178733001;178733000	chr2:179597729;179597728;179597727
N2A	4148	12667;12668;12669	chr2:178733002;178733001;178733000	chr2:179597729;179597728;179597727
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-37
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1549
• 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
K/R	rs794729609	None	0.999	N	0.614	0.327	0.374076547971	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs794729609	None	0.999	N	0.614	0.327	0.374076547971	gnomAD-4.0.0	2.56299E-06	None	None	None	None	N	None	3.38364E-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
K/A	0.87	likely_pathogenic	0.9142	pathogenic	-1.141	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
K/C	0.8447	likely_pathogenic	0.8903	pathogenic	-1.111	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
K/D	0.9784	likely_pathogenic	0.987	pathogenic	-0.341	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
K/E	0.6844	likely_pathogenic	0.7615	pathogenic	-0.152	Destabilizing	0.999	D	0.572	neutral	D	0.533070928	None	None	N
K/F	0.9207	likely_pathogenic	0.9456	pathogenic	-0.78	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
K/G	0.9306	likely_pathogenic	0.9577	pathogenic	-1.56	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/H	0.4231	ambiguous	0.4706	ambiguous	-1.789	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/I	0.7374	likely_pathogenic	0.7956	pathogenic	-0.012	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
K/L	0.6526	likely_pathogenic	0.7214	pathogenic	-0.012	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/M	0.5609	ambiguous	0.6354	pathogenic	-0.121	Destabilizing	1.0	D	0.811	deleterious	N	0.487063049	None	None	N
K/N	0.9064	likely_pathogenic	0.9381	pathogenic	-0.902	Destabilizing	1.0	D	0.715	prob.delet.	N	0.514713183	None	None	N
K/P	0.9911	likely_pathogenic	0.9947	pathogenic	-0.361	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/Q	0.3031	likely_benign	0.3569	ambiguous	-0.831	Destabilizing	1.0	D	0.717	prob.delet.	N	0.496101949	None	None	N
K/R	0.0737	likely_benign	0.0799	benign	-0.712	Destabilizing	0.999	D	0.614	neutral	N	0.507064156	None	None	N
K/S	0.8973	likely_pathogenic	0.9331	pathogenic	-1.697	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
K/T	0.7992	likely_pathogenic	0.8615	pathogenic	-1.256	Destabilizing	1.0	D	0.793	deleterious	N	0.514459694	None	None	N
K/V	0.7218	likely_pathogenic	0.783	pathogenic	-0.361	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
K/W	0.8569	likely_pathogenic	0.8991	pathogenic	-0.606	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
K/Y	0.8301	likely_pathogenic	0.87	pathogenic	-0.307	Destabilizing	1.0	D	0.893	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.