TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33667	101224;101225;101226	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
N2AB	32026	96301;96302;96303	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
N2A	31099	93520;93521;93522	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
N2B	24602	74029;74030;74031	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
Novex-1	24727	74404;74405;74406	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
Novex-2	24794	74605;74606;74607	chr2:178535616;178535615;178535614	chr2:179400343;179400342;179400341
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-159
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.082
• 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/C	rs1296330425	-0.796	1.0	D	0.891	0.818	0.892787688341	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/C	rs1296330425	-0.796	1.0	D	0.891	0.818	0.892787688341	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
Y/A	0.9974	likely_pathogenic	0.996	pathogenic	-1.734	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/C	0.959	likely_pathogenic	0.9418	pathogenic	-1.147	Destabilizing	1.0	D	0.891	deleterious	D	0.613258911	None	None	N
Y/D	0.999	likely_pathogenic	0.9984	pathogenic	-2.691	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.613258911	None	None	N
Y/E	0.9996	likely_pathogenic	0.9992	pathogenic	-2.449	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
Y/F	0.2651	likely_benign	0.3036	benign	-0.517	Destabilizing	1.0	D	0.659	neutral	D	0.579000342	None	None	N
Y/G	0.9953	likely_pathogenic	0.9932	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/H	0.9825	likely_pathogenic	0.975	pathogenic	-1.901	Destabilizing	1.0	D	0.791	deleterious	D	0.613057107	None	None	N
Y/I	0.9707	likely_pathogenic	0.9555	pathogenic	-0.321	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9991	pathogenic	-1.698	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/L	0.9068	likely_pathogenic	0.8673	pathogenic	-0.321	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
Y/M	0.9893	likely_pathogenic	0.985	pathogenic	-0.422	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/N	0.995	likely_pathogenic	0.9923	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.613258911	None	None	N
Y/P	0.9987	likely_pathogenic	0.998	pathogenic	-0.806	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
Y/Q	0.9993	likely_pathogenic	0.9988	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/R	0.9966	likely_pathogenic	0.9945	pathogenic	-2.211	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/S	0.9934	likely_pathogenic	0.9892	pathogenic	-2.836	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.613258911	None	None	N
Y/T	0.9971	likely_pathogenic	0.9954	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/V	0.9519	likely_pathogenic	0.9345	pathogenic	-0.806	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/W	0.8455	likely_pathogenic	0.831	pathogenic	-0.037	Destabilizing	1.0	D	0.78	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.