TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6199	18820;18821;18822	chr2:178729561;178729560;178729559	chr2:179594288;179594287;179594286
N2AB	5882	17869;17870;17871	chr2:178729561;178729560;178729559	chr2:179594288;179594287;179594286
N2A	4955	15088;15089;15090	chr2:178729561;178729560;178729559	chr2:179594288;179594287;179594286
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-46
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1424
• 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/A	None	None	0.996	D	0.811	0.635	0.675111477399	gnomAD-4.0.0	1.59492E-06	None	None	None	None	N	None	0	0	None	0	2.775E-05	None	0	0	0	0	0
P/L	rs758776829	0.257	0.999	D	0.875	0.612	0.907606656126	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6681	likely_pathogenic	0.6654	pathogenic	-1.682	Destabilizing	0.996	D	0.811	deleterious	D	0.604243774	None	None	N
P/C	0.9775	likely_pathogenic	0.9803	pathogenic	-1.598	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/D	0.9983	likely_pathogenic	0.9981	pathogenic	-1.125	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/E	0.9937	likely_pathogenic	0.9923	pathogenic	-1.022	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/F	0.9965	likely_pathogenic	0.9967	pathogenic	-1.208	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/G	0.9783	likely_pathogenic	0.9793	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/H	0.9918	likely_pathogenic	0.9909	pathogenic	-1.642	Destabilizing	1.0	D	0.857	deleterious	D	0.642227695	None	None	N
P/I	0.93	likely_pathogenic	0.945	pathogenic	-0.593	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
P/K	0.9952	likely_pathogenic	0.994	pathogenic	-1.106	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/L	0.8501	likely_pathogenic	0.8567	pathogenic	-0.593	Destabilizing	0.999	D	0.875	deleterious	D	0.604647382	None	None	N
P/M	0.9742	likely_pathogenic	0.979	pathogenic	-0.771	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/N	0.9966	likely_pathogenic	0.9964	pathogenic	-1.104	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/Q	0.9858	likely_pathogenic	0.983	pathogenic	-1.116	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/R	0.983	likely_pathogenic	0.9811	pathogenic	-0.877	Destabilizing	0.999	D	0.883	deleterious	D	0.642227695	None	None	N
P/S	0.9537	likely_pathogenic	0.9498	pathogenic	-1.866	Destabilizing	0.998	D	0.838	deleterious	D	0.641824087	None	None	N
P/T	0.9317	likely_pathogenic	0.9273	pathogenic	-1.62	Destabilizing	0.884	D	0.709	prob.delet.	D	0.62600653	None	None	N
P/V	0.8441	likely_pathogenic	0.8659	pathogenic	-0.924	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
P/W	0.9991	likely_pathogenic	0.9992	pathogenic	-1.411	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/Y	0.9979	likely_pathogenic	0.9979	pathogenic	-1.067	Destabilizing	1.0	D	0.882	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.