TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26509	79750;79751;79752	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
N2AB	24868	74827;74828;74829	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
N2A	23941	72046;72047;72048	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
N2B	17444	52555;52556;52557	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
Novex-1	17569	52930;52931;52932	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
Novex-2	17636	53131;53132;53133	chr2:178566607;178566606;178566605	chr2:179431334;179431333;179431332
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: Fn3-81
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.1849
• Predicted PPI site: I

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	rs1705957839	None	0.062	N	0.474	0.207	0.158396225186	gnomAD-4.0.0	1.59437E-06	None	None	None	None	I	None	5.66059E-05	0	None	0	0	None	0	0	0	0	0
G/S	rs1311507525	-1.028	None	N	0.249	0.055	0.0666544352282	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
G/S	rs1311507525	-1.028	None	N	0.249	0.055	0.0666544352282	gnomAD-4.0.0	1.16413E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.52921E-05	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	0.1254	likely_benign	0.1229	benign	-0.697	Destabilizing	0.027	N	0.408	neutral	N	0.452659241	None	None	I
G/C	0.1561	likely_benign	0.1576	benign	-0.895	Destabilizing	0.78	D	0.593	neutral	N	0.492217707	None	None	I
G/D	0.4556	ambiguous	0.4666	ambiguous	-2.002	Highly Destabilizing	0.062	N	0.474	neutral	N	0.414986288	None	None	I
G/E	0.4043	ambiguous	0.4331	ambiguous	-1.916	Destabilizing	0.081	N	0.5	neutral	None	None	None	None	I
G/F	0.6441	likely_pathogenic	0.6313	pathogenic	-0.884	Destabilizing	0.555	D	0.598	neutral	None	None	None	None	I
G/H	0.4831	ambiguous	0.488	ambiguous	-1.919	Destabilizing	0.001	N	0.402	neutral	None	None	None	None	I
G/I	0.3059	likely_benign	0.2928	benign	0.165	Stabilizing	0.38	N	0.598	neutral	None	None	None	None	I
G/K	0.6631	likely_pathogenic	0.6986	pathogenic	-1.348	Destabilizing	0.081	N	0.506	neutral	None	None	None	None	I
G/L	0.4098	ambiguous	0.4103	ambiguous	0.165	Stabilizing	0.149	N	0.561	neutral	None	None	None	None	I
G/M	0.4281	ambiguous	0.438	ambiguous	0.16	Stabilizing	0.935	D	0.588	neutral	None	None	None	None	I
G/N	0.2443	likely_benign	0.2422	benign	-1.318	Destabilizing	0.081	N	0.473	neutral	None	None	None	None	I
G/P	0.945	likely_pathogenic	0.9464	pathogenic	-0.078	Destabilizing	0.38	N	0.557	neutral	None	None	None	None	I
G/Q	0.423	ambiguous	0.4474	ambiguous	-1.271	Destabilizing	0.38	N	0.557	neutral	None	None	None	None	I
G/R	0.5238	ambiguous	0.5546	ambiguous	-1.313	Destabilizing	0.317	N	0.557	neutral	N	0.445751912	None	None	I
G/S	0.0759	likely_benign	0.0744	benign	-1.57	Destabilizing	None	N	0.249	neutral	N	0.389722484	None	None	I
G/T	0.1371	likely_benign	0.1386	benign	-1.384	Destabilizing	0.081	N	0.498	neutral	None	None	None	None	I
G/V	0.2117	likely_benign	0.1979	benign	-0.078	Destabilizing	0.317	N	0.575	neutral	N	0.45937457	None	None	I
G/W	0.5335	ambiguous	0.5613	ambiguous	-1.642	Destabilizing	0.935	D	0.597	neutral	None	None	None	None	I
G/Y	0.4834	ambiguous	0.4791	ambiguous	-1.052	Destabilizing	0.38	N	0.579	neutral	None	None	None	None	I

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.