TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31442	94549;94550;94551	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
N2AB	29801	89626;89627;89628	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
N2A	28874	86845;86846;86847	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
N2B	22377	67354;67355;67356	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
Novex-1	22502	67729;67730;67731	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
Novex-2	22569	67930;67931;67932	chr2:178547201;178547200;178547199	chr2:179411928;179411927;179411926
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: Fn3-117
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0802
• 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/A	None	None	1.0	N	0.592	0.498	0.463501289208	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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	0.6019	likely_pathogenic	0.6327	pathogenic	-0.31	Destabilizing	1.0	D	0.592	neutral	N	0.511445771	None	None	N
G/C	0.8932	likely_pathogenic	0.9201	pathogenic	-0.24	Destabilizing	1.0	D	0.809	deleterious	N	0.506636832	None	None	N
G/D	0.9877	likely_pathogenic	0.9915	pathogenic	-1.518	Destabilizing	1.0	D	0.838	deleterious	N	0.50692632	None	None	N
G/E	0.9911	likely_pathogenic	0.9946	pathogenic	-1.354	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/F	0.9932	likely_pathogenic	0.9952	pathogenic	-0.332	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/H	0.9891	likely_pathogenic	0.9926	pathogenic	-1.608	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
G/I	0.994	likely_pathogenic	0.9968	pathogenic	0.715	Stabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/K	0.9963	likely_pathogenic	0.9977	pathogenic	-0.567	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/L	0.9904	likely_pathogenic	0.9934	pathogenic	0.715	Stabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/M	0.9932	likely_pathogenic	0.9955	pathogenic	0.515	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/N	0.9755	likely_pathogenic	0.9828	pathogenic	-0.741	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/P	0.9997	likely_pathogenic	0.9998	pathogenic	0.417	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/Q	0.9843	likely_pathogenic	0.9897	pathogenic	-0.546	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/R	0.9825	likely_pathogenic	0.9887	pathogenic	-0.844	Destabilizing	1.0	D	0.877	deleterious	N	0.495454656	None	None	N
G/S	0.5726	likely_pathogenic	0.6059	pathogenic	-1.027	Destabilizing	1.0	D	0.661	neutral	N	0.489921248	None	None	N
G/T	0.9534	likely_pathogenic	0.9696	pathogenic	-0.758	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/V	0.9854	likely_pathogenic	0.9915	pathogenic	0.417	Stabilizing	1.0	D	0.893	deleterious	D	0.530057005	None	None	N
G/W	0.987	likely_pathogenic	0.9921	pathogenic	-1.233	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/Y	0.9823	likely_pathogenic	0.9881	pathogenic	-0.534	Destabilizing	1.0	D	0.853	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.