TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30550	91873;91874;91875	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
N2AB	28909	86950;86951;86952	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
N2A	27982	84169;84170;84171	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
N2B	21485	64678;64679;64680	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
Novex-1	21610	65053;65054;65055	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
Novex-2	21677	65254;65255;65256	chr2:178550190;178550189;178550188	chr2:179414917;179414916;179414915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-149
• Domain position: 19
• Structural Position: 35
• Q(SASA): 0.2878
• 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/I	None	None	0.001	N	0.27	0.196	0.392395365052	gnomAD-4.0.0	1.59137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43287E-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	0.7288	likely_pathogenic	0.7246	pathogenic	-0.718	Destabilizing	0.003	N	0.265	neutral	N	0.503515789	None	None	I
V/C	0.8621	likely_pathogenic	0.8678	pathogenic	-0.704	Destabilizing	0.981	D	0.693	prob.neutral	None	None	None	None	I
V/D	0.9925	likely_pathogenic	0.9908	pathogenic	-0.178	Destabilizing	0.818	D	0.769	deleterious	None	None	None	None	I
V/E	0.9728	likely_pathogenic	0.9671	pathogenic	-0.263	Destabilizing	0.324	N	0.702	prob.neutral	D	0.603409786	None	None	I
V/F	0.5122	ambiguous	0.5078	ambiguous	-0.808	Destabilizing	0.69	D	0.731	prob.delet.	None	None	None	None	I
V/G	0.8606	likely_pathogenic	0.851	pathogenic	-0.909	Destabilizing	0.324	N	0.707	prob.neutral	D	0.577871674	None	None	I
V/H	0.9768	likely_pathogenic	0.973	pathogenic	-0.526	Destabilizing	0.981	D	0.768	deleterious	None	None	None	None	I
V/I	0.0819	likely_benign	0.0848	benign	-0.348	Destabilizing	0.001	N	0.27	neutral	N	0.479540064	None	None	I
V/K	0.9709	likely_pathogenic	0.9642	pathogenic	-0.525	Destabilizing	0.008	N	0.447	neutral	None	None	None	None	I
V/L	0.3531	ambiguous	0.3608	ambiguous	-0.348	Destabilizing	0.033	N	0.475	neutral	N	0.519963112	None	None	I
V/M	0.444	ambiguous	0.4434	ambiguous	-0.357	Destabilizing	0.69	D	0.601	neutral	None	None	None	None	I
V/N	0.9675	likely_pathogenic	0.9624	pathogenic	-0.226	Destabilizing	0.818	D	0.788	deleterious	None	None	None	None	I
V/P	0.9732	likely_pathogenic	0.9712	pathogenic	-0.435	Destabilizing	0.818	D	0.741	deleterious	None	None	None	None	I
V/Q	0.9505	likely_pathogenic	0.9407	pathogenic	-0.44	Destabilizing	0.69	D	0.76	deleterious	None	None	None	None	I
V/R	0.9487	likely_pathogenic	0.9383	pathogenic	-0.073	Destabilizing	0.527	D	0.767	deleterious	None	None	None	None	I
V/S	0.8898	likely_pathogenic	0.8745	pathogenic	-0.69	Destabilizing	0.241	N	0.672	neutral	None	None	None	None	I
V/T	0.7619	likely_pathogenic	0.7299	pathogenic	-0.663	Destabilizing	0.388	N	0.563	neutral	None	None	None	None	I
V/W	0.9736	likely_pathogenic	0.974	pathogenic	-0.892	Destabilizing	0.981	D	0.767	deleterious	None	None	None	None	I
V/Y	0.9126	likely_pathogenic	0.9012	pathogenic	-0.583	Destabilizing	0.818	D	0.734	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.