TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34340	103243;103244;103245	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
N2AB	32699	98320;98321;98322	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
N2A	31772	95539;95540;95541	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
N2B	25275	76048;76049;76050	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
Novex-1	25400	76423;76424;76425	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
Novex-2	25467	76624;76625;76626	chr2:178533597;178533596;178533595	chr2:179398324;179398323;179398322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-161
• Domain position: 83
• Structural Position: 164
• Q(SASA): 0.2339
• 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/A	rs1211065675	-0.39	1.0	D	0.756	0.813	0.518312163451	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
G/A	rs1211065675	-0.39	1.0	D	0.756	0.813	0.518312163451	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	0	2.773E-05	None	0	0	0	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
G/A	0.9303	likely_pathogenic	0.9026	pathogenic	-0.54	Destabilizing	1.0	D	0.756	deleterious	D	0.607104778	None	None	I
G/C	0.9828	likely_pathogenic	0.9784	pathogenic	-0.954	Destabilizing	1.0	D	0.804	deleterious	D	0.645694113	None	None	I
G/D	0.9882	likely_pathogenic	0.9784	pathogenic	-1.082	Destabilizing	1.0	D	0.851	deleterious	D	0.606701169	None	None	I
G/E	0.9925	likely_pathogenic	0.9873	pathogenic	-1.237	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/F	0.9972	likely_pathogenic	0.9969	pathogenic	-1.165	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/H	0.9954	likely_pathogenic	0.9937	pathogenic	-0.844	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/I	0.9973	likely_pathogenic	0.9963	pathogenic	-0.597	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/K	0.9927	likely_pathogenic	0.9894	pathogenic	-1.23	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/L	0.9956	likely_pathogenic	0.995	pathogenic	-0.597	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/M	0.9979	likely_pathogenic	0.9974	pathogenic	-0.561	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/N	0.9922	likely_pathogenic	0.9891	pathogenic	-0.817	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
G/P	0.9996	likely_pathogenic	0.9996	pathogenic	-0.543	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/Q	0.9895	likely_pathogenic	0.9849	pathogenic	-1.136	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.9737	likely_pathogenic	0.9658	pathogenic	-0.689	Destabilizing	1.0	D	0.855	deleterious	D	0.607306582	None	None	I
G/S	0.8895	likely_pathogenic	0.8622	pathogenic	-0.917	Destabilizing	1.0	D	0.805	deleterious	D	0.598605767	None	None	I
G/T	0.9892	likely_pathogenic	0.9827	pathogenic	-1.016	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/V	0.9943	likely_pathogenic	0.9925	pathogenic	-0.543	Destabilizing	1.0	D	0.828	deleterious	D	0.645290504	None	None	I
G/W	0.9918	likely_pathogenic	0.9907	pathogenic	-1.332	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/Y	0.9957	likely_pathogenic	0.9952	pathogenic	-1.014	Destabilizing	1.0	D	0.831	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.