TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32261	97006;97007;97008	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
N2AB	30620	92083;92084;92085	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
N2A	29693	89302;89303;89304	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
N2B	23196	69811;69812;69813	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
Novex-1	23321	70186;70187;70188	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
Novex-2	23388	70387;70388;70389	chr2:178543192;178543191;178543190	chr2:179407919;179407918;179407917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-123
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.3047
• 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	rs1060500578	None	0.77	N	0.495	0.335	0.352693368174	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/G	rs1060500578	None	0.77	N	0.495	0.335	0.352693368174	gnomAD-4.0.0	4.05999E-06	None	None	None	None	N	None	0	6.15612E-05	None	0	0	None	0	0	3.61483E-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
E/A	0.1695	likely_benign	0.1713	benign	-0.675	Destabilizing	0.501	D	0.383	neutral	N	0.4843103	None	None	N
E/C	0.7671	likely_pathogenic	0.7723	pathogenic	-0.412	Destabilizing	0.991	D	0.625	neutral	None	None	None	None	N
E/D	0.2525	likely_benign	0.2444	benign	-0.87	Destabilizing	None	N	0.189	neutral	N	0.493161857	None	None	N
E/F	0.7465	likely_pathogenic	0.7477	pathogenic	0.045	Stabilizing	0.946	D	0.601	neutral	None	None	None	None	N
E/G	0.2132	likely_benign	0.2149	benign	-1.027	Destabilizing	0.77	D	0.495	neutral	N	0.489313475	None	None	N
E/H	0.3667	ambiguous	0.3789	ambiguous	0.048	Stabilizing	0.013	N	0.362	neutral	None	None	None	None	N
E/I	0.4073	ambiguous	0.4086	ambiguous	0.282	Stabilizing	0.891	D	0.599	neutral	None	None	None	None	N
E/K	0.1667	likely_benign	0.1728	benign	-0.259	Destabilizing	0.482	N	0.322	neutral	N	0.472535868	None	None	N
E/L	0.403	ambiguous	0.4068	ambiguous	0.282	Stabilizing	0.536	D	0.573	neutral	None	None	None	None	N
E/M	0.4514	ambiguous	0.4544	ambiguous	0.502	Stabilizing	0.944	D	0.587	neutral	None	None	None	None	N
E/N	0.3253	likely_benign	0.3252	benign	-0.907	Destabilizing	0.212	N	0.303	neutral	None	None	None	None	N
E/P	0.902	likely_pathogenic	0.902	pathogenic	-0.015	Destabilizing	0.549	D	0.542	neutral	None	None	None	None	N
E/Q	0.0951	likely_benign	0.1007	benign	-0.762	Destabilizing	0.049	N	0.208	neutral	N	0.463030951	None	None	N
E/R	0.217	likely_benign	0.2331	benign	0.134	Stabilizing	0.711	D	0.366	neutral	None	None	None	None	N
E/S	0.1787	likely_benign	0.1836	benign	-1.153	Destabilizing	0.571	D	0.321	neutral	None	None	None	None	N
E/T	0.1926	likely_benign	0.1939	benign	-0.851	Destabilizing	0.647	D	0.419	neutral	None	None	None	None	N
E/V	0.2286	likely_benign	0.2283	benign	-0.015	Destabilizing	0.815	D	0.572	neutral	N	0.508072594	None	None	N
E/W	0.8671	likely_pathogenic	0.8735	pathogenic	0.357	Stabilizing	0.998	D	0.652	neutral	None	None	None	None	N
E/Y	0.5936	likely_pathogenic	0.6042	pathogenic	0.326	Stabilizing	0.958	D	0.595	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.