TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8470	25633;25634;25635	chr2:178717326;178717325;178717324	chr2:179582053;179582052;179582051
N2AB	8153	24682;24683;24684	chr2:178717326;178717325;178717324	chr2:179582053;179582052;179582051
N2A	7226	21901;21902;21903	chr2:178717326;178717325;178717324	chr2:179582053;179582052;179582051
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-70
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3279
• 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	0.998	D	0.681	0.681	0.641104024009	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-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	0.3924	ambiguous	0.3796	ambiguous	-0.274	Destabilizing	0.998	D	0.681	prob.neutral	D	0.638916669	None	None	N
G/C	0.796	likely_pathogenic	0.7452	pathogenic	-0.868	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/D	0.6489	likely_pathogenic	0.5468	ambiguous	-0.425	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/E	0.6686	likely_pathogenic	0.5914	pathogenic	-0.589	Destabilizing	1.0	D	0.771	deleterious	D	0.598500378	None	None	N
G/F	0.9061	likely_pathogenic	0.8759	pathogenic	-0.964	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/H	0.7992	likely_pathogenic	0.7388	pathogenic	-0.51	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/I	0.9001	likely_pathogenic	0.8801	pathogenic	-0.412	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/K	0.8815	likely_pathogenic	0.8359	pathogenic	-0.779	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/L	0.7679	likely_pathogenic	0.7635	pathogenic	-0.412	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/M	0.8443	likely_pathogenic	0.8307	pathogenic	-0.467	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/N	0.5296	ambiguous	0.4692	ambiguous	-0.415	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
G/P	0.9793	likely_pathogenic	0.9745	pathogenic	-0.333	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/Q	0.6942	likely_pathogenic	0.6438	pathogenic	-0.7	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/R	0.7651	likely_pathogenic	0.7005	pathogenic	-0.352	Destabilizing	0.991	D	0.653	neutral	D	0.622866948	None	None	N
G/S	0.2162	likely_benign	0.2081	benign	-0.583	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/T	0.5278	ambiguous	0.4996	ambiguous	-0.676	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/V	0.7872	likely_pathogenic	0.7582	pathogenic	-0.333	Destabilizing	1.0	D	0.783	deleterious	D	0.632587503	None	None	N
G/W	0.8038	likely_pathogenic	0.7574	pathogenic	-1.11	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/Y	0.8513	likely_pathogenic	0.7969	pathogenic	-0.764	Destabilizing	1.0	D	0.804	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.