TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27242	81949;81950;81951	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
N2AB	25601	77026;77027;77028	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
N2A	24674	74245;74246;74247	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
N2B	18177	54754;54755;54756	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
Novex-1	18302	55129;55130;55131	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
Novex-2	18369	55330;55331;55332	chr2:178564408;178564407;178564406	chr2:179429135;179429134;179429133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-86
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2813
• 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
E/G	None	None	1.0	N	0.759	0.522	0.566919426312	gnomAD-4.0.0	1.36873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79906E-06	0	0
E/V	rs1210575101	1.259	1.0	N	0.777	0.53	0.487843537783	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/V	rs1210575101	1.259	1.0	N	0.777	0.53	0.487843537783	gnomAD-4.0.0	6.84363E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15947E-05	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
E/A	0.6303	likely_pathogenic	0.5479	ambiguous	-0.642	Destabilizing	0.999	D	0.699	prob.neutral	N	0.488551668	None	None	N
E/C	0.9599	likely_pathogenic	0.9547	pathogenic	0.039	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/D	0.5971	likely_pathogenic	0.6303	pathogenic	-1.144	Destabilizing	0.999	D	0.585	neutral	N	0.469068288	None	None	N
E/F	0.9819	likely_pathogenic	0.9754	pathogenic	-0.098	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
E/G	0.8623	likely_pathogenic	0.8109	pathogenic	-1.109	Destabilizing	1.0	D	0.759	deleterious	N	0.516063672	None	None	N
E/H	0.9418	likely_pathogenic	0.9254	pathogenic	-0.139	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/I	0.8456	likely_pathogenic	0.8162	pathogenic	0.685	Stabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
E/K	0.8444	likely_pathogenic	0.7752	pathogenic	-0.329	Destabilizing	0.999	D	0.657	neutral	D	0.522521971	None	None	N
E/L	0.9173	likely_pathogenic	0.8982	pathogenic	0.685	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/M	0.8777	likely_pathogenic	0.8441	pathogenic	1.341	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/N	0.8577	likely_pathogenic	0.8389	pathogenic	-0.854	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/P	0.9987	likely_pathogenic	0.9984	pathogenic	0.262	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.4322	ambiguous	0.3554	ambiguous	-0.526	Destabilizing	1.0	D	0.705	prob.neutral	N	0.469900995	None	None	N
E/R	0.8884	likely_pathogenic	0.8476	pathogenic	-0.318	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/S	0.6972	likely_pathogenic	0.6383	pathogenic	-1.467	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/T	0.8007	likely_pathogenic	0.7578	pathogenic	-1.016	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/V	0.7057	likely_pathogenic	0.661	pathogenic	0.262	Stabilizing	1.0	D	0.777	deleterious	N	0.475687652	None	None	N
E/W	0.9951	likely_pathogenic	0.9944	pathogenic	-0.059	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Y	0.9665	likely_pathogenic	0.9593	pathogenic	0.205	Stabilizing	1.0	D	0.805	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.