TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4977	15154;15155;15156	chr2:178735517;178735516;178735515	chr2:179600244;179600243;179600242
N2AB	4660	14203;14204;14205	chr2:178735517;178735516;178735515	chr2:179600244;179600243;179600242
N2A	3733	11422;11423;11424	chr2:178735517;178735516;178735515	chr2:179600244;179600243;179600242
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-32
• Domain position: 90
• Structural Position: 178
• Q(SASA): 1.0619
• 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
V/A	None	None	0.334	D	0.661	0.676	0.764842827521	gnomAD-4.0.0	7.03072E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.12019E-07	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
V/A	0.5388	ambiguous	0.6124	pathogenic	-1.441	Destabilizing	0.334	N	0.661	neutral	D	0.798283987	None	None	I
V/C	0.868	likely_pathogenic	0.8882	pathogenic	-1.468	Destabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	I
V/D	0.9651	likely_pathogenic	0.9752	pathogenic	-1.742	Destabilizing	0.781	D	0.713	prob.delet.	D	0.797535789	None	None	I
V/E	0.9225	likely_pathogenic	0.9413	pathogenic	-1.755	Destabilizing	0.826	D	0.68	prob.neutral	None	None	None	None	I
V/F	0.4186	ambiguous	0.4451	ambiguous	-1.384	Destabilizing	0.638	D	0.704	prob.neutral	D	0.762959346	None	None	I
V/G	0.7219	likely_pathogenic	0.7879	pathogenic	-1.71	Destabilizing	0.781	D	0.689	prob.neutral	D	0.797535789	None	None	I
V/H	0.9646	likely_pathogenic	0.9746	pathogenic	-1.189	Destabilizing	0.982	D	0.732	prob.delet.	None	None	None	None	I
V/I	0.0644	likely_benign	0.0638	benign	-0.8	Destabilizing	0.002	N	0.506	neutral	D	0.586427915	None	None	I
V/K	0.948	likely_pathogenic	0.9628	pathogenic	-1.091	Destabilizing	0.826	D	0.679	prob.neutral	None	None	None	None	I
V/L	0.2288	likely_benign	0.2482	benign	-0.8	Destabilizing	0.034	N	0.671	neutral	D	0.698486935	None	None	I
V/M	0.2406	likely_benign	0.2645	benign	-0.768	Destabilizing	0.7	D	0.733	prob.delet.	None	None	None	None	I
V/N	0.8497	likely_pathogenic	0.8921	pathogenic	-1.026	Destabilizing	0.935	D	0.723	prob.delet.	None	None	None	None	I
V/P	0.896	likely_pathogenic	0.9224	pathogenic	-0.982	Destabilizing	0.935	D	0.687	prob.neutral	None	None	None	None	I
V/Q	0.9093	likely_pathogenic	0.9339	pathogenic	-1.286	Destabilizing	0.935	D	0.7	prob.neutral	None	None	None	None	I
V/R	0.9203	likely_pathogenic	0.9426	pathogenic	-0.589	Destabilizing	0.826	D	0.723	prob.delet.	None	None	None	None	I
V/S	0.7121	likely_pathogenic	0.7809	pathogenic	-1.529	Destabilizing	0.826	D	0.664	neutral	None	None	None	None	I
V/T	0.5866	likely_pathogenic	0.6614	pathogenic	-1.437	Destabilizing	0.399	N	0.695	prob.neutral	None	None	None	None	I
V/W	0.9655	likely_pathogenic	0.9713	pathogenic	-1.504	Destabilizing	0.982	D	0.697	prob.neutral	None	None	None	None	I
V/Y	0.8908	likely_pathogenic	0.9089	pathogenic	-1.17	Destabilizing	0.826	D	0.71	prob.delet.	None	None	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.