TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7393	22402;22403;22404	chr2:178722722;178722721;178722720	chr2:179587449;179587448;179587447
N2AB	7076	21451;21452;21453	chr2:178722722;178722721;178722720	chr2:179587449;179587448;179587447
N2A	6149	18670;18671;18672	chr2:178722722;178722721;178722720	chr2:179587449;179587448;179587447
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-58
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1069
• 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
Y/D	rs1185905654	None	1.0	D	0.881	0.857	0.893575084684	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/D	rs1185905654	None	1.0	D	0.881	0.857	0.893575084684	gnomAD-4.0.0	6.57748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47106E-05	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
Y/A	0.991	likely_pathogenic	0.9975	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/C	0.935	likely_pathogenic	0.9831	pathogenic	-1.624	Destabilizing	1.0	D	0.843	deleterious	D	0.653423396	None	None	N
Y/D	0.9957	likely_pathogenic	0.9987	pathogenic	-2.68	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.653423396	None	None	N
Y/E	0.9976	likely_pathogenic	0.9992	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/F	0.2083	likely_benign	0.3459	ambiguous	-0.756	Destabilizing	1.0	D	0.668	neutral	D	0.569945921	None	None	N
Y/G	0.9865	likely_pathogenic	0.995	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/H	0.9737	likely_pathogenic	0.9924	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.705	prob.neutral	D	0.653221591	None	None	N
Y/I	0.7621	likely_pathogenic	0.878	pathogenic	-0.618	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.9992	pathogenic	-1.73	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/L	0.7857	likely_pathogenic	0.8756	pathogenic	-0.618	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
Y/M	0.9268	likely_pathogenic	0.9731	pathogenic	-0.814	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/N	0.9721	likely_pathogenic	0.9896	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.653423396	None	None	N
Y/P	0.9983	likely_pathogenic	0.9994	pathogenic	-1.133	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/Q	0.9975	likely_pathogenic	0.9994	pathogenic	-2.15	Highly Destabilizing	0.978	D	0.647	neutral	None	None	None	None	N
Y/R	0.9943	likely_pathogenic	0.9979	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/S	0.988	likely_pathogenic	0.9964	pathogenic	-2.954	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.653423396	None	None	N
Y/T	0.9912	likely_pathogenic	0.9975	pathogenic	-2.551	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/V	0.7446	likely_pathogenic	0.8697	pathogenic	-1.133	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
Y/W	0.87	likely_pathogenic	0.9342	pathogenic	-0.146	Destabilizing	1.0	D	0.691	prob.neutral	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.