TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7306	22141;22142;22143	chr2:178723091;178723090;178723089	chr2:179587818;179587817;179587816
N2AB	6989	21190;21191;21192	chr2:178723091;178723090;178723089	chr2:179587818;179587817;179587816
N2A	6062	18409;18410;18411	chr2:178723091;178723090;178723089	chr2:179587818;179587817;179587816
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-57
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1747
• 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/Y	rs773636793	-0.628	1.0	D	0.753	0.672	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
N/Y	rs773636793	-0.628	1.0	D	0.753	0.672	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
N/Y	rs773636793	-0.628	1.0	D	0.753	0.672	None	gnomAD-4.0.0	6.40695E-06	None	None	None	None	N	None	8.45966E-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
N/A	0.9905	likely_pathogenic	0.9905	pathogenic	-0.453	Destabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	N
N/C	0.9804	likely_pathogenic	0.9791	pathogenic	0.008	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
N/D	0.9262	likely_pathogenic	0.9272	pathogenic	-1.392	Destabilizing	0.998	D	0.605	neutral	D	0.524279652	None	None	N
N/E	0.9914	likely_pathogenic	0.9916	pathogenic	-1.341	Destabilizing	0.997	D	0.618	neutral	None	None	None	None	N
N/F	0.9985	likely_pathogenic	0.9985	pathogenic	-0.599	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/G	0.9619	likely_pathogenic	0.9601	pathogenic	-0.714	Destabilizing	0.998	D	0.562	neutral	None	None	None	None	N
N/H	0.9689	likely_pathogenic	0.9651	pathogenic	-0.715	Destabilizing	1.0	D	0.705	prob.neutral	D	0.5255471	None	None	N
N/I	0.9872	likely_pathogenic	0.988	pathogenic	0.179	Stabilizing	1.0	D	0.762	deleterious	D	0.552298635	None	None	N
N/K	0.9948	likely_pathogenic	0.9944	pathogenic	-0.102	Destabilizing	0.767	D	0.373	neutral	D	0.551538167	None	None	N
N/L	0.9822	likely_pathogenic	0.9818	pathogenic	0.179	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
N/M	0.9825	likely_pathogenic	0.9828	pathogenic	0.722	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/P	0.9974	likely_pathogenic	0.9968	pathogenic	-0.003	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
N/Q	0.9957	likely_pathogenic	0.9956	pathogenic	-0.984	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
N/R	0.995	likely_pathogenic	0.9944	pathogenic	0.023	Stabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
N/S	0.7958	likely_pathogenic	0.7815	pathogenic	-0.609	Destabilizing	0.996	D	0.554	neutral	N	0.503186429	None	None	N
N/T	0.9099	likely_pathogenic	0.9102	pathogenic	-0.412	Destabilizing	0.998	D	0.653	neutral	N	0.514822678	None	None	N
N/V	0.9868	likely_pathogenic	0.9874	pathogenic	-0.003	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
N/W	0.9991	likely_pathogenic	0.9991	pathogenic	-0.485	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
N/Y	0.9787	likely_pathogenic	0.9764	pathogenic	-0.155	Destabilizing	1.0	D	0.753	deleterious	D	0.552045146	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.