TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4779	14560;14561;14562	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
N2AB	4462	13609;13610;13611	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
N2A	3535	10828;10829;10830	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
N2B	4416	13471;13472;13473	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
Novex-1	4541	13846;13847;13848	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
Novex-2	4608	14047;14048;14049	chr2:178738118;178738117;178738116	chr2:179602845;179602844;179602843
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-30
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2533
• 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
G/D	None	None	1.0	D	0.835	0.771	0.551593237191	gnomAD-4.0.0	1.59144E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02425E-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
G/A	0.7322	likely_pathogenic	0.8592	pathogenic	-0.385	Destabilizing	1.0	D	0.749	deleterious	D	0.69022132	None	None	I
G/C	0.9171	likely_pathogenic	0.959	pathogenic	-0.978	Destabilizing	1.0	D	0.789	deleterious	D	0.838748861	None	None	I
G/D	0.9018	likely_pathogenic	0.953	pathogenic	-0.517	Destabilizing	1.0	D	0.835	deleterious	D	0.687846681	None	None	I
G/E	0.9396	likely_pathogenic	0.9739	pathogenic	-0.679	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/F	0.9844	likely_pathogenic	0.9917	pathogenic	-1.094	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/H	0.9686	likely_pathogenic	0.9854	pathogenic	-0.558	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/I	0.976	likely_pathogenic	0.9903	pathogenic	-0.541	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/K	0.9648	likely_pathogenic	0.9835	pathogenic	-0.804	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/L	0.9741	likely_pathogenic	0.988	pathogenic	-0.541	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/M	0.9869	likely_pathogenic	0.9944	pathogenic	-0.557	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/N	0.9311	likely_pathogenic	0.9656	pathogenic	-0.503	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/P	0.9966	likely_pathogenic	0.998	pathogenic	-0.457	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/Q	0.9404	likely_pathogenic	0.972	pathogenic	-0.79	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/R	0.9051	likely_pathogenic	0.9495	pathogenic	-0.353	Destabilizing	1.0	D	0.845	deleterious	D	0.759208855	None	None	I
G/S	0.5786	likely_pathogenic	0.7248	pathogenic	-0.67	Destabilizing	1.0	D	0.803	deleterious	D	0.706517345	None	None	I
G/T	0.9119	likely_pathogenic	0.9555	pathogenic	-0.761	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/V	0.9561	likely_pathogenic	0.9813	pathogenic	-0.457	Destabilizing	1.0	D	0.809	deleterious	D	0.805342699	None	None	I
G/W	0.9784	likely_pathogenic	0.9882	pathogenic	-1.214	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/Y	0.9754	likely_pathogenic	0.9878	pathogenic	-0.881	Destabilizing	1.0	D	0.815	deleterious	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.