TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5098	15517;15518;15519	chr2:178734532;178734531;178734530	chr2:179599259;179599258;179599257
N2AB	4781	14566;14567;14568	chr2:178734532;178734531;178734530	chr2:179599259;179599258;179599257
N2A	3854	11785;11786;11787	chr2:178734532;178734531;178734530	chr2:179599259;179599258;179599257
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-34
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1215
• 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	rs1349400261	-1.709	0.104	D	0.68	0.361	0.544432747571	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
V/A	rs1349400261	-1.709	0.104	D	0.68	0.361	0.544432747571	gnomAD-4.0.0	6.16535E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.10272E-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
V/A	0.6218	likely_pathogenic	0.472	ambiguous	-1.805	Destabilizing	0.104	N	0.68	prob.neutral	D	0.533333951	None	None	N
V/C	0.8868	likely_pathogenic	0.8309	pathogenic	-1.659	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
V/D	0.9791	likely_pathogenic	0.9667	pathogenic	-1.553	Destabilizing	0.667	D	0.868	deleterious	D	0.727294211	None	None	N
V/E	0.9542	likely_pathogenic	0.9339	pathogenic	-1.348	Destabilizing	0.726	D	0.843	deleterious	None	None	None	None	N
V/F	0.2787	likely_benign	0.2099	benign	-1.081	Destabilizing	0.497	N	0.833	deleterious	D	0.684270324	None	None	N
V/G	0.8082	likely_pathogenic	0.7198	pathogenic	-2.333	Highly Destabilizing	0.667	D	0.849	deleterious	D	0.705628519	None	None	N
V/H	0.9705	likely_pathogenic	0.9487	pathogenic	-1.996	Destabilizing	0.968	D	0.846	deleterious	None	None	None	None	N
V/I	0.0549	likely_benign	0.0548	benign	-0.355	Destabilizing	None	N	0.181	neutral	D	0.527445535	None	None	N
V/K	0.9619	likely_pathogenic	0.9362	pathogenic	-1.303	Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
V/L	0.1569	likely_benign	0.1231	benign	-0.355	Destabilizing	0.009	N	0.397	neutral	D	0.537371855	None	None	N
V/M	0.2335	likely_benign	0.1694	benign	-0.615	Destabilizing	0.033	N	0.477	neutral	None	None	None	None	N
V/N	0.9145	likely_pathogenic	0.8543	pathogenic	-1.535	Destabilizing	0.89	D	0.866	deleterious	None	None	None	None	N
V/P	0.9515	likely_pathogenic	0.9183	pathogenic	-0.809	Destabilizing	0.89	D	0.844	deleterious	None	None	None	None	N
V/Q	0.9481	likely_pathogenic	0.9176	pathogenic	-1.364	Destabilizing	0.726	D	0.835	deleterious	None	None	None	None	N
V/R	0.9403	likely_pathogenic	0.9031	pathogenic	-1.252	Destabilizing	0.726	D	0.871	deleterious	None	None	None	None	N
V/S	0.8404	likely_pathogenic	0.7411	pathogenic	-2.314	Highly Destabilizing	0.726	D	0.833	deleterious	None	None	None	None	N
V/T	0.7051	likely_pathogenic	0.5761	pathogenic	-1.945	Destabilizing	0.272	N	0.707	prob.neutral	None	None	None	None	N
V/W	0.9478	likely_pathogenic	0.9267	pathogenic	-1.434	Destabilizing	0.968	D	0.841	deleterious	None	None	None	None	N
V/Y	0.8249	likely_pathogenic	0.7589	pathogenic	-1.055	Destabilizing	0.726	D	0.818	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.