TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25703	77332;77333;77334	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
N2AB	24062	72409;72410;72411	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
N2A	23135	69628;69629;69630	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
N2B	16638	50137;50138;50139	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
Novex-1	16763	50512;50513;50514	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
Novex-2	16830	50713;50714;50715	chr2:178569025;178569024;178569023	chr2:179433752;179433751;179433750
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: Fn3-75
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.19
• 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/R	None	None	0.931	N	0.688	0.169	0.445007932271	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79928E-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	0.2102	likely_benign	0.21	benign	-0.613	Destabilizing	0.993	D	0.689	prob.neutral	N	0.469976433	None	None	N
G/C	0.4586	ambiguous	0.4421	ambiguous	-0.891	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
G/D	0.6532	likely_pathogenic	0.5928	pathogenic	-1.77	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
G/E	0.5016	ambiguous	0.4278	ambiguous	-1.696	Destabilizing	1.0	D	0.848	deleterious	N	0.498007529	None	None	N
G/F	0.8575	likely_pathogenic	0.8443	pathogenic	-0.733	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/H	0.7859	likely_pathogenic	0.7444	pathogenic	-1.706	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/I	0.6677	likely_pathogenic	0.6199	pathogenic	0.175	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/K	0.7673	likely_pathogenic	0.7169	pathogenic	-1.323	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
G/L	0.6418	likely_pathogenic	0.6215	pathogenic	0.175	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/M	0.7163	likely_pathogenic	0.6973	pathogenic	0.04	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/N	0.6214	likely_pathogenic	0.5876	pathogenic	-1.282	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/P	0.975	likely_pathogenic	0.9677	pathogenic	-0.043	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/Q	0.548	ambiguous	0.5077	ambiguous	-1.254	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/R	0.6271	likely_pathogenic	0.5556	ambiguous	-1.258	Destabilizing	0.931	D	0.688	prob.neutral	N	0.498180887	None	None	N
G/S	0.1784	likely_benign	0.1651	benign	-1.538	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
G/T	0.4015	ambiguous	0.3535	ambiguous	-1.367	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
G/V	0.4864	ambiguous	0.4363	ambiguous	-0.043	Destabilizing	1.0	D	0.881	deleterious	N	0.47214248	None	None	N
G/W	0.8074	likely_pathogenic	0.7628	pathogenic	-1.437	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/Y	0.797	likely_pathogenic	0.7686	pathogenic	-0.853	Destabilizing	1.0	D	0.868	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.