TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8719	26380;26381;26382	chr2:178715031;178715030;178715029	chr2:179579758;179579757;179579756
N2AB	8402	25429;25430;25431	chr2:178715031;178715030;178715029	chr2:179579758;179579757;179579756
N2A	7475	22648;22649;22650	chr2:178715031;178715030;178715029	chr2:179579758;179579757;179579756
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-72
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.155
• Predicted PPI site: I

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/D	rs770551201	-1.16	0.879	D	0.58	0.49	0.263140351381	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
N/D	rs770551201	-1.16	0.879	D	0.58	0.49	0.263140351381	gnomAD-4.0.0	2.05336E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6992E-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
N/A	0.966	likely_pathogenic	0.9909	pathogenic	-0.833	Destabilizing	0.609	D	0.694	prob.neutral	None	None	None	None	I
N/C	0.9322	likely_pathogenic	0.9737	pathogenic	-0.167	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
N/D	0.9024	likely_pathogenic	0.9692	pathogenic	-1.249	Destabilizing	0.879	D	0.58	neutral	D	0.543206828	None	None	I
N/E	0.9947	likely_pathogenic	0.9978	pathogenic	-1.14	Destabilizing	0.97	D	0.656	neutral	None	None	None	None	I
N/F	0.9981	likely_pathogenic	0.9994	pathogenic	-0.619	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	I
N/G	0.9201	likely_pathogenic	0.9684	pathogenic	-1.168	Destabilizing	0.988	D	0.536	neutral	None	None	None	None	I
N/H	0.9349	likely_pathogenic	0.9756	pathogenic	-0.966	Destabilizing	0.999	D	0.711	prob.delet.	D	0.555830581	None	None	I
N/I	0.9829	likely_pathogenic	0.9951	pathogenic	0.023	Stabilizing	0.992	D	0.797	deleterious	D	0.55608407	None	None	I
N/K	0.9944	likely_pathogenic	0.9981	pathogenic	-0.316	Destabilizing	0.989	D	0.663	neutral	D	0.555323602	None	None	I
N/L	0.9477	likely_pathogenic	0.9828	pathogenic	0.023	Stabilizing	0.987	D	0.773	deleterious	None	None	None	None	I
N/M	0.9774	likely_pathogenic	0.9928	pathogenic	0.5	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
N/P	0.9933	likely_pathogenic	0.9973	pathogenic	-0.233	Destabilizing	0.986	D	0.788	deleterious	None	None	None	None	I
N/Q	0.9932	likely_pathogenic	0.9975	pathogenic	-1.048	Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	I
N/R	0.9916	likely_pathogenic	0.9963	pathogenic	-0.318	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
N/S	0.3882	ambiguous	0.6282	pathogenic	-0.966	Destabilizing	0.786	D	0.517	neutral	N	0.501376004	None	None	I
N/T	0.8181	likely_pathogenic	0.9359	pathogenic	-0.681	Destabilizing	0.034	N	0.311	neutral	D	0.543460317	None	None	I
N/V	0.9663	likely_pathogenic	0.9896	pathogenic	-0.233	Destabilizing	0.868	D	0.775	deleterious	None	None	None	None	I
N/W	0.9988	likely_pathogenic	0.9996	pathogenic	-0.416	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
N/Y	0.979	likely_pathogenic	0.9934	pathogenic	-0.155	Destabilizing	0.999	D	0.8	deleterious	D	0.555830581	None	None	I

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.