TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20800	62623;62624;62625	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
N2AB	19159	57700;57701;57702	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
N2A	18232	54919;54920;54921	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
N2B	11735	35428;35429;35430	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
Novex-1	11860	35803;35804;35805	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
Novex-2	11927	36004;36005;36006	chr2:178589327;178589326;178589325	chr2:179454054;179454053;179454052
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: Ig-122
• Domain position: 32
• Structural Position: 45
• Q(SASA): 0.6624
• 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
E/G	rs1404277332	-0.449	0.822	N	0.608	0.337	0.465294738428	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/G	rs1404277332	-0.449	0.822	N	0.608	0.337	0.465294738428	gnomAD-4.0.0	1.59335E-06	None	None	None	None	I	None	0	0	None	0	2.7767E-05	None	0	0	0	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	0.144	likely_benign	0.1303	benign	-0.134	Destabilizing	0.822	D	0.595	neutral	N	0.508625246	None	None	I
E/C	0.8324	likely_pathogenic	0.8465	pathogenic	-0.093	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
E/D	0.115	likely_benign	0.1236	benign	-0.323	Destabilizing	0.014	N	0.311	neutral	N	0.488441975	None	None	I
E/F	0.7625	likely_pathogenic	0.7425	pathogenic	-0.063	Destabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	I
E/G	0.2712	likely_benign	0.2416	benign	-0.307	Destabilizing	0.822	D	0.608	neutral	N	0.499623664	None	None	I
E/H	0.4534	ambiguous	0.4286	ambiguous	0.345	Stabilizing	0.998	D	0.61	neutral	None	None	None	None	I
E/I	0.2786	likely_benign	0.2663	benign	0.276	Stabilizing	0.956	D	0.733	prob.delet.	None	None	None	None	I
E/K	0.1859	likely_benign	0.158	benign	0.418	Stabilizing	0.822	D	0.571	neutral	N	0.475800752	None	None	I
E/L	0.3419	ambiguous	0.3242	benign	0.276	Stabilizing	0.956	D	0.659	neutral	None	None	None	None	I
E/M	0.4271	ambiguous	0.4052	ambiguous	0.15	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	I
E/N	0.2119	likely_benign	0.2093	benign	0.107	Stabilizing	0.915	D	0.6	neutral	None	None	None	None	I
E/P	0.9087	likely_pathogenic	0.9022	pathogenic	0.159	Stabilizing	0.978	D	0.676	prob.neutral	None	None	None	None	I
E/Q	0.1414	likely_benign	0.1286	benign	0.139	Stabilizing	0.942	D	0.604	neutral	N	0.472741804	None	None	I
E/R	0.3394	likely_benign	0.2877	benign	0.66	Stabilizing	0.978	D	0.616	neutral	None	None	None	None	I
E/S	0.1773	likely_benign	0.1675	benign	-0.034	Destabilizing	0.754	D	0.553	neutral	None	None	None	None	I
E/T	0.1547	likely_benign	0.1417	benign	0.109	Stabilizing	0.16	N	0.383	neutral	None	None	None	None	I
E/V	0.1563	likely_benign	0.1472	benign	0.159	Stabilizing	0.942	D	0.605	neutral	N	0.50978004	None	None	I
E/W	0.9338	likely_pathogenic	0.9272	pathogenic	0.036	Stabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	I
E/Y	0.6644	likely_pathogenic	0.6526	pathogenic	0.175	Stabilizing	0.993	D	0.723	prob.delet.	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.