TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6693	20302;20303;20304	chr2:178727288;178727287;178727286	chr2:179592015;179592014;179592013
N2AB	6376	19351;19352;19353	chr2:178727288;178727287;178727286	chr2:179592015;179592014;179592013
N2A	5449	16570;16571;16572	chr2:178727288;178727287;178727286	chr2:179592015;179592014;179592013
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-51
• Domain position: 27
• Structural Position: 40
• Q(SASA): 0.4348
• 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/V	None	None	1.0	D	0.763	0.598	0.804695419218	gnomAD-4.0.0	1.59303E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43419E-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
G/A	0.6055	likely_pathogenic	0.4974	ambiguous	-0.394	Destabilizing	1.0	D	0.76	deleterious	D	0.575073185	None	None	I
G/C	0.9502	likely_pathogenic	0.9332	pathogenic	-0.84	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
G/D	0.9826	likely_pathogenic	0.979	pathogenic	-0.833	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/E	0.9888	likely_pathogenic	0.9854	pathogenic	-0.977	Destabilizing	1.0	D	0.79	deleterious	D	0.603236547	None	None	I
G/F	0.9922	likely_pathogenic	0.991	pathogenic	-1.022	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
G/H	0.9948	likely_pathogenic	0.9941	pathogenic	-0.816	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
G/I	0.9803	likely_pathogenic	0.9703	pathogenic	-0.404	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/K	0.9957	likely_pathogenic	0.9953	pathogenic	-1.117	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/L	0.9873	likely_pathogenic	0.9827	pathogenic	-0.404	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/M	0.9941	likely_pathogenic	0.9917	pathogenic	-0.44	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
G/N	0.9866	likely_pathogenic	0.984	pathogenic	-0.683	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/P	0.9959	likely_pathogenic	0.9923	pathogenic	-0.364	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/Q	0.9913	likely_pathogenic	0.9895	pathogenic	-0.951	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/R	0.9833	likely_pathogenic	0.9825	pathogenic	-0.671	Destabilizing	1.0	D	0.791	deleterious	D	0.606869024	None	None	I
G/S	0.6917	likely_pathogenic	0.6152	pathogenic	-0.806	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/T	0.9382	likely_pathogenic	0.9055	pathogenic	-0.883	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/V	0.9456	likely_pathogenic	0.9197	pathogenic	-0.364	Destabilizing	1.0	D	0.763	deleterious	D	0.632407136	None	None	I
G/W	0.99	likely_pathogenic	0.9896	pathogenic	-1.247	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
G/Y	0.9917	likely_pathogenic	0.9911	pathogenic	-0.888	Destabilizing	1.0	D	0.733	prob.delet.	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.