TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19960	60103;60104;60105	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
N2AB	18319	55180;55181;55182	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
N2A	17392	52399;52400;52401	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
N2B	10895	32908;32909;32910	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
Novex-1	11020	33283;33284;33285	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
Novex-2	11087	33484;33485;33486	chr2:178592026;178592025;178592024	chr2:179456753;179456752;179456751
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: Fn3-32
• Domain position: 84
• Structural Position: 118
• Q(SASA): 0.1474
• 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
G/C	None	None	0.999	D	0.824	0.546	0.778462375712	gnomAD-4.0.0	6.84536E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99661E-07	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	0.5977	likely_pathogenic	0.6581	pathogenic	-0.799	Destabilizing	0.64	D	0.7	prob.neutral	D	0.537941633	None	None	N
G/C	0.8849	likely_pathogenic	0.9013	pathogenic	-0.89	Destabilizing	0.999	D	0.824	deleterious	D	0.538955591	None	None	N
G/D	0.9824	likely_pathogenic	0.9829	pathogenic	-1.813	Destabilizing	0.896	D	0.776	deleterious	N	0.515736001	None	None	N
G/E	0.9859	likely_pathogenic	0.9863	pathogenic	-1.787	Destabilizing	0.976	D	0.773	deleterious	None	None	None	None	N
G/F	0.9908	likely_pathogenic	0.9908	pathogenic	-0.858	Destabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
G/H	0.9895	likely_pathogenic	0.9911	pathogenic	-1.631	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
G/I	0.9792	likely_pathogenic	0.9795	pathogenic	-0.162	Destabilizing	0.976	D	0.822	deleterious	None	None	None	None	N
G/K	0.9969	likely_pathogenic	0.9969	pathogenic	-1.319	Destabilizing	0.976	D	0.777	deleterious	None	None	None	None	N
G/L	0.9768	likely_pathogenic	0.9771	pathogenic	-0.162	Destabilizing	0.976	D	0.811	deleterious	None	None	None	None	N
G/M	0.9851	likely_pathogenic	0.986	pathogenic	-0.203	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
G/N	0.9705	likely_pathogenic	0.9734	pathogenic	-1.138	Destabilizing	0.919	D	0.751	deleterious	None	None	None	None	N
G/P	0.9979	likely_pathogenic	0.9975	pathogenic	-0.333	Destabilizing	0.988	D	0.779	deleterious	None	None	None	None	N
G/Q	0.9886	likely_pathogenic	0.9896	pathogenic	-1.22	Destabilizing	0.988	D	0.769	deleterious	None	None	None	None	N
G/R	0.9931	likely_pathogenic	0.9931	pathogenic	-1.128	Destabilizing	0.968	D	0.779	deleterious	D	0.537434654	None	None	N
G/S	0.3343	likely_benign	0.4084	ambiguous	-1.381	Destabilizing	0.046	N	0.432	neutral	N	0.449398011	None	None	N
G/T	0.8709	likely_pathogenic	0.8949	pathogenic	-1.281	Destabilizing	0.132	N	0.68	prob.neutral	None	None	None	None	N
G/V	0.9594	likely_pathogenic	0.9614	pathogenic	-0.333	Destabilizing	0.968	D	0.803	deleterious	D	0.538448612	None	None	N
G/W	0.9873	likely_pathogenic	0.9875	pathogenic	-1.422	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
G/Y	0.9857	likely_pathogenic	0.9881	pathogenic	-0.946	Destabilizing	0.996	D	0.82	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.