TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7729	23410;23411;23412	chr2:178720577;178720576;178720575	chr2:179585304;179585303;179585302
N2AB	7412	22459;22460;22461	chr2:178720577;178720576;178720575	chr2:179585304;179585303;179585302
N2A	6485	19678;19679;19680	chr2:178720577;178720576;178720575	chr2:179585304;179585303;179585302
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-62
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.271
• 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
P/L	None	None	0.928	D	0.452	0.583	0.781312296865	gnomAD-4.0.0	6.84418E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65755E-05

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
P/A	0.1564	likely_benign	0.1567	benign	-1.114	Destabilizing	0.012	N	0.153	neutral	N	0.515866084	None	None	I
P/C	0.9175	likely_pathogenic	0.9114	pathogenic	-0.685	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	I
P/D	0.9046	likely_pathogenic	0.9057	pathogenic	-1.089	Destabilizing	0.401	N	0.515	neutral	None	None	None	None	I
P/E	0.6923	likely_pathogenic	0.6913	pathogenic	-1.084	Destabilizing	0.515	D	0.469	neutral	None	None	None	None	I
P/F	0.8745	likely_pathogenic	0.8729	pathogenic	-0.888	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	I
P/G	0.5962	likely_pathogenic	0.6003	pathogenic	-1.379	Destabilizing	0.585	D	0.401	neutral	None	None	None	None	I
P/H	0.6285	likely_pathogenic	0.6324	pathogenic	-0.804	Destabilizing	0.999	D	0.534	neutral	D	0.601563187	None	None	I
P/I	0.7588	likely_pathogenic	0.7542	pathogenic	-0.49	Destabilizing	0.944	D	0.579	neutral	None	None	None	None	I
P/K	0.755	likely_pathogenic	0.7668	pathogenic	-0.928	Destabilizing	0.971	D	0.502	neutral	None	None	None	None	I
P/L	0.374	ambiguous	0.3749	ambiguous	-0.49	Destabilizing	0.928	D	0.452	neutral	D	0.606902974	None	None	I
P/M	0.7085	likely_pathogenic	0.7011	pathogenic	-0.551	Destabilizing	0.989	D	0.547	neutral	None	None	None	None	I
P/N	0.8288	likely_pathogenic	0.8289	pathogenic	-0.769	Destabilizing	0.937	D	0.547	neutral	None	None	None	None	I
P/Q	0.4914	ambiguous	0.4963	ambiguous	-0.908	Destabilizing	0.989	D	0.523	neutral	None	None	None	None	I
P/R	0.6192	likely_pathogenic	0.6391	pathogenic	-0.454	Destabilizing	0.995	D	0.553	neutral	D	0.612999975	None	None	I
P/S	0.3148	likely_benign	0.3177	benign	-1.168	Destabilizing	0.217	N	0.195	neutral	D	0.531652935	None	None	I
P/T	0.3755	ambiguous	0.3755	ambiguous	-1.055	Destabilizing	0.614	D	0.391	neutral	D	0.587694028	None	None	I
P/V	0.6099	likely_pathogenic	0.6064	pathogenic	-0.666	Destabilizing	0.074	N	0.227	neutral	None	None	None	None	I
P/W	0.9573	likely_pathogenic	0.9539	pathogenic	-1.062	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
P/Y	0.8576	likely_pathogenic	0.8589	pathogenic	-0.752	Destabilizing	0.999	D	0.592	neutral	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.