TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26354	79285;79286;79287	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
N2AB	24713	74362;74363;74364	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
N2A	23786	71581;71582;71583	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
N2B	17289	52090;52091;52092	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
Novex-1	17414	52465;52466;52467	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
Novex-2	17481	52666;52667;52668	chr2:178567072;178567071;178567070	chr2:179431799;179431798;179431797
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: Fn3-79
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3112
• 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/D	rs1706180054	None	1.0	N	0.805	0.626	0.316198179892	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs1706180054	None	1.0	N	0.805	0.626	0.316198179892	gnomAD-4.0.0	2.03006E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40993E-06	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	0.6267	likely_pathogenic	0.6194	pathogenic	-0.539	Destabilizing	1.0	D	0.713	prob.delet.	N	0.501561177	None	None	N
G/C	0.6811	likely_pathogenic	0.7058	pathogenic	-0.928	Destabilizing	1.0	D	0.81	deleterious	D	0.555926848	None	None	N
G/D	0.5277	ambiguous	0.5447	ambiguous	-0.927	Destabilizing	1.0	D	0.805	deleterious	N	0.477011687	None	None	N
G/E	0.7561	likely_pathogenic	0.7568	pathogenic	-1.06	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/F	0.9403	likely_pathogenic	0.9302	pathogenic	-1.074	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/H	0.8186	likely_pathogenic	0.8122	pathogenic	-0.865	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/I	0.953	likely_pathogenic	0.9501	pathogenic	-0.477	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/K	0.8908	likely_pathogenic	0.8987	pathogenic	-1.165	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
G/L	0.9302	likely_pathogenic	0.9223	pathogenic	-0.477	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/M	0.914	likely_pathogenic	0.9059	pathogenic	-0.418	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/N	0.3845	ambiguous	0.3706	ambiguous	-0.779	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/P	0.9959	likely_pathogenic	0.995	pathogenic	-0.46	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
G/Q	0.7979	likely_pathogenic	0.7956	pathogenic	-1.063	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
G/R	0.8491	likely_pathogenic	0.8664	pathogenic	-0.668	Destabilizing	1.0	D	0.845	deleterious	D	0.52519884	None	None	N
G/S	0.3147	likely_benign	0.3191	benign	-0.96	Destabilizing	1.0	D	0.797	deleterious	N	0.509434762	None	None	N
G/T	0.6938	likely_pathogenic	0.6765	pathogenic	-1.025	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
G/V	0.9035	likely_pathogenic	0.9022	pathogenic	-0.46	Destabilizing	1.0	D	0.833	deleterious	D	0.537315614	None	None	N
G/W	0.8844	likely_pathogenic	0.8856	pathogenic	-1.28	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/Y	0.85	likely_pathogenic	0.8462	pathogenic	-0.933	Destabilizing	1.0	D	0.801	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.