TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16975	51148;51149;51150	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
N2AB	15334	46225;46226;46227	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
N2A	14407	43444;43445;43446	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
N2B	7910	23953;23954;23955	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
Novex-1	8035	24328;24329;24330	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
Novex-2	8102	24529;24530;24531	chr2:178611206;178611205;178611204	chr2:179475933;179475932;179475931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-111
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4681
• 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
P/S	None	None	0.322	N	0.372	0.147	0.267299060538	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.0887	likely_benign	0.086	benign	-1.292	Destabilizing	0.885	D	0.51	neutral	N	0.506495901	None	None	I
P/C	0.5347	ambiguous	0.4847	ambiguous	-0.917	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
P/D	0.4125	ambiguous	0.3724	ambiguous	-1.153	Destabilizing	0.986	D	0.686	prob.neutral	None	None	None	None	I
P/E	0.321	likely_benign	0.2888	benign	-1.155	Destabilizing	0.953	D	0.61	neutral	None	None	None	None	I
P/F	0.4949	ambiguous	0.4785	ambiguous	-0.982	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
P/G	0.3514	ambiguous	0.3334	benign	-1.598	Destabilizing	0.91	D	0.597	neutral	None	None	None	None	I
P/H	0.2141	likely_benign	0.1933	benign	-1.079	Destabilizing	0.999	D	0.684	prob.neutral	N	0.509575668	None	None	I
P/I	0.2886	likely_benign	0.2796	benign	-0.558	Destabilizing	0.993	D	0.734	prob.delet.	None	None	None	None	I
P/K	0.2973	likely_benign	0.2747	benign	-1.21	Destabilizing	0.386	N	0.373	neutral	None	None	None	None	I
P/L	0.1396	likely_benign	0.1306	benign	-0.558	Destabilizing	0.982	D	0.686	prob.neutral	N	0.50662802	None	None	I
P/M	0.3265	likely_benign	0.3172	benign	-0.481	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	I
P/N	0.336	likely_benign	0.3232	benign	-1.01	Destabilizing	0.986	D	0.705	prob.neutral	None	None	None	None	I
P/Q	0.2027	likely_benign	0.1858	benign	-1.155	Destabilizing	0.986	D	0.716	prob.delet.	None	None	None	None	I
P/R	0.207	likely_benign	0.186	benign	-0.674	Destabilizing	0.964	D	0.704	prob.neutral	N	0.492249935	None	None	I
P/S	0.1479	likely_benign	0.1336	benign	-1.489	Destabilizing	0.322	N	0.372	neutral	N	0.493308401	None	None	I
P/T	0.1123	likely_benign	0.1008	benign	-1.375	Destabilizing	0.885	D	0.621	neutral	N	0.481182998	None	None	I
P/V	0.2088	likely_benign	0.1989	benign	-0.767	Destabilizing	0.986	D	0.666	neutral	None	None	None	None	I
P/W	0.7033	likely_pathogenic	0.6691	pathogenic	-1.166	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
P/Y	0.49	ambiguous	0.4655	ambiguous	-0.878	Destabilizing	0.999	D	0.709	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.