TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2808	8647;8648;8649	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
N2AB	2808	8647;8648;8649	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
N2A	2808	8647;8648;8649	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
N2B	2762	8509;8510;8511	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
Novex-1	2762	8509;8510;8511	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
Novex-2	2762	8509;8510;8511	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004
Novex-3	2808	8647;8648;8649	chr2:178770279;178770278;178770277	chr2:179635006;179635005;179635004

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-18
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.1554
• 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/K	rs2154342769	None	0.351	N	0.203	0.283	0.207176502487	gnomAD-4.0.0	1.59048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.3557	ambiguous	0.3792	ambiguous	-0.719	Destabilizing	0.101	N	0.32	neutral	N	0.444804059	None	None	N
E/C	0.9676	likely_pathogenic	0.9684	pathogenic	-0.21	Destabilizing	0.983	D	0.35	neutral	None	None	None	None	N
E/D	0.6343	likely_pathogenic	0.6452	pathogenic	-0.592	Destabilizing	0.351	N	0.219	neutral	N	0.480585929	None	None	N
E/F	0.9764	likely_pathogenic	0.9774	pathogenic	-0.408	Destabilizing	0.716	D	0.422	neutral	None	None	None	None	N
E/G	0.5128	ambiguous	0.5073	ambiguous	-0.983	Destabilizing	0.001	N	0.167	neutral	D	0.609271905	None	None	N
E/H	0.9083	likely_pathogenic	0.9115	pathogenic	-0.416	Destabilizing	0.94	D	0.271	neutral	None	None	None	None	N
E/I	0.7281	likely_pathogenic	0.7525	pathogenic	-0.032	Destabilizing	0.129	N	0.369	neutral	None	None	None	None	N
E/K	0.5057	ambiguous	0.5025	ambiguous	-0.013	Destabilizing	0.351	N	0.203	neutral	N	0.477670025	None	None	N
E/L	0.7745	likely_pathogenic	0.7812	pathogenic	-0.032	Destabilizing	0.001	N	0.209	neutral	None	None	None	None	N
E/M	0.8067	likely_pathogenic	0.8273	pathogenic	0.25	Stabilizing	0.061	N	0.253	neutral	None	None	None	None	N
E/N	0.8052	likely_pathogenic	0.8218	pathogenic	-0.435	Destabilizing	0.418	N	0.282	neutral	None	None	None	None	N
E/P	0.8411	likely_pathogenic	0.8611	pathogenic	-0.241	Destabilizing	0.94	D	0.368	neutral	None	None	None	None	N
E/Q	0.2715	likely_benign	0.2909	benign	-0.369	Destabilizing	0.523	D	0.296	neutral	N	0.514247804	None	None	N
E/R	0.6988	likely_pathogenic	0.6877	pathogenic	0.208	Stabilizing	0.836	D	0.289	neutral	None	None	None	None	N
E/S	0.616	likely_pathogenic	0.6505	pathogenic	-0.634	Destabilizing	0.418	N	0.192	neutral	None	None	None	None	N
E/T	0.6968	likely_pathogenic	0.7204	pathogenic	-0.415	Destabilizing	0.418	N	0.309	neutral	None	None	None	None	N
E/V	0.5068	ambiguous	0.5278	ambiguous	-0.241	Destabilizing	0.003	N	0.141	neutral	N	0.455463333	None	None	N
E/W	0.9936	likely_pathogenic	0.9923	pathogenic	-0.166	Destabilizing	0.983	D	0.377	neutral	None	None	None	None	N
E/Y	0.9636	likely_pathogenic	0.9605	pathogenic	-0.151	Destabilizing	0.94	D	0.374	neutral	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.