TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28417	85474;85475;85476	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
N2AB	26776	80551;80552;80553	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
N2A	25849	77770;77771;77772	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
N2B	19352	58279;58280;58281	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
Novex-1	19477	58654;58655;58656	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
Novex-2	19544	58855;58856;58857	chr2:178560883;178560882;178560881	chr2:179425610;179425609;179425608
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-143
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1813
• 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
V/A	None	None	0.892	D	0.612	0.608	0.729265719692	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-05	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	0.6636	likely_pathogenic	0.6153	pathogenic	-2.145	Highly Destabilizing	0.892	D	0.612	neutral	D	0.529818239	None	None	N
V/C	0.8908	likely_pathogenic	0.8722	pathogenic	-1.784	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
V/D	0.9334	likely_pathogenic	0.9086	pathogenic	-2.786	Highly Destabilizing	0.994	D	0.814	deleterious	D	0.530578708	None	None	N
V/E	0.8542	likely_pathogenic	0.8122	pathogenic	-2.675	Highly Destabilizing	0.996	D	0.798	deleterious	None	None	None	None	N
V/F	0.4515	ambiguous	0.4247	ambiguous	-1.43	Destabilizing	0.967	D	0.761	deleterious	N	0.502724309	None	None	N
V/G	0.7488	likely_pathogenic	0.6987	pathogenic	-2.588	Highly Destabilizing	0.983	D	0.811	deleterious	D	0.530578708	None	None	N
V/H	0.927	likely_pathogenic	0.9014	pathogenic	-2.185	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/I	0.0823	likely_benign	0.0797	benign	-0.952	Destabilizing	0.025	N	0.281	neutral	N	0.390645204	None	None	N
V/K	0.8481	likely_pathogenic	0.803	pathogenic	-1.919	Destabilizing	0.987	D	0.799	deleterious	None	None	None	None	N
V/L	0.3042	likely_benign	0.2968	benign	-0.952	Destabilizing	0.369	N	0.531	neutral	D	0.524514632	None	None	N
V/M	0.2677	likely_benign	0.2505	benign	-0.866	Destabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
V/N	0.8271	likely_pathogenic	0.7621	pathogenic	-2.009	Highly Destabilizing	0.996	D	0.836	deleterious	None	None	None	None	N
V/P	0.9833	likely_pathogenic	0.9815	pathogenic	-1.32	Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
V/Q	0.8136	likely_pathogenic	0.7682	pathogenic	-2.045	Highly Destabilizing	0.996	D	0.826	deleterious	None	None	None	None	N
V/R	0.7973	likely_pathogenic	0.7553	pathogenic	-1.465	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
V/S	0.7669	likely_pathogenic	0.7064	pathogenic	-2.567	Highly Destabilizing	0.987	D	0.796	deleterious	None	None	None	None	N
V/T	0.7306	likely_pathogenic	0.6574	pathogenic	-2.337	Highly Destabilizing	0.916	D	0.705	prob.neutral	None	None	None	None	N
V/W	0.9608	likely_pathogenic	0.9492	pathogenic	-1.828	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/Y	0.8556	likely_pathogenic	0.8384	pathogenic	-1.539	Destabilizing	0.987	D	0.756	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.