TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15736	47431;47432;47433	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
N2AB	14095	42508;42509;42510	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
N2A	13168	39727;39728;39729	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
N2B	6671	20236;20237;20238	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
Novex-1	6796	20611;20612;20613	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
Novex-2	6863	20812;20813;20814	chr2:178618252;178618251;178618250	chr2:179482979;179482978;179482977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-1
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1048
• 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
N/S	rs2057709379	None	0.999	D	0.601	0.55	0.37762505005	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs2057709379	None	0.999	D	0.601	0.55	0.37762505005	gnomAD-4.0.0	6.58129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47249E-05	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
N/A	0.9991	likely_pathogenic	0.9989	pathogenic	-1.039	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/C	0.9855	likely_pathogenic	0.9768	pathogenic	-0.815	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
N/D	0.9943	likely_pathogenic	0.9935	pathogenic	-2.314	Highly Destabilizing	0.999	D	0.617	neutral	D	0.704930067	None	None	N
N/E	0.9989	likely_pathogenic	0.9991	pathogenic	-2.128	Highly Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
N/F	0.9997	likely_pathogenic	0.9997	pathogenic	-0.842	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
N/G	0.9949	likely_pathogenic	0.994	pathogenic	-1.355	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
N/H	0.9944	likely_pathogenic	0.9922	pathogenic	-0.967	Destabilizing	1.0	D	0.777	deleterious	D	0.755809705	None	None	N
N/I	0.9977	likely_pathogenic	0.9973	pathogenic	-0.221	Destabilizing	1.0	D	0.808	deleterious	D	0.789419873	None	None	N
N/K	0.9992	likely_pathogenic	0.9992	pathogenic	-0.462	Destabilizing	1.0	D	0.762	deleterious	D	0.787236883	None	None	N
N/L	0.9939	likely_pathogenic	0.9931	pathogenic	-0.221	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
N/M	0.9976	likely_pathogenic	0.9971	pathogenic	-0.056	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
N/P	0.9992	likely_pathogenic	0.9992	pathogenic	-0.468	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
N/Q	0.9994	likely_pathogenic	0.9993	pathogenic	-1.282	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/R	0.9988	likely_pathogenic	0.9989	pathogenic	-0.444	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
N/S	0.9648	likely_pathogenic	0.9461	pathogenic	-1.317	Destabilizing	0.999	D	0.601	neutral	D	0.670937537	None	None	N
N/T	0.9877	likely_pathogenic	0.9767	pathogenic	-0.98	Destabilizing	0.999	D	0.729	prob.delet.	D	0.602402385	None	None	N
N/V	0.9974	likely_pathogenic	0.9971	pathogenic	-0.468	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.817	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
N/Y	0.9965	likely_pathogenic	0.9962	pathogenic	-0.427	Destabilizing	1.0	D	0.821	deleterious	D	0.755809705	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.