TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22533	67822;67823;67824	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
N2AB	20892	62899;62900;62901	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
N2A	19965	60118;60119;60120	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
N2B	13468	40627;40628;40629	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
Novex-1	13593	41002;41003;41004	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
Novex-2	13660	41203;41204;41205	chr2:178579600;178579599;178579598	chr2:179444327;179444326;179444325
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-51
• Domain position: 83
• Structural Position: 119
• Q(SASA): 0.4825
• 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
T/I	rs2047233269	None	0.939	N	0.533	0.286	0.350524144436	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
T/A	0.0722	likely_benign	0.0703	benign	-0.523	Destabilizing	0.012	N	0.107	neutral	N	0.383972734	None	None	N
T/C	0.324	likely_benign	0.3229	benign	-0.234	Destabilizing	0.996	D	0.504	neutral	None	None	None	None	N
T/D	0.2273	likely_benign	0.2393	benign	-0.025	Destabilizing	0.742	D	0.524	neutral	None	None	None	None	N
T/E	0.1623	likely_benign	0.1645	benign	-0.117	Destabilizing	0.742	D	0.455	neutral	None	None	None	None	N
T/F	0.1469	likely_benign	0.1598	benign	-1.106	Destabilizing	0.953	D	0.48	neutral	None	None	None	None	N
T/G	0.2281	likely_benign	0.2297	benign	-0.621	Destabilizing	0.373	N	0.451	neutral	None	None	None	None	N
T/H	0.1861	likely_benign	0.1958	benign	-1.012	Destabilizing	0.996	D	0.487	neutral	None	None	None	None	N
T/I	0.0793	likely_benign	0.0817	benign	-0.382	Destabilizing	0.939	D	0.533	neutral	N	0.445869342	None	None	N
T/K	0.1262	likely_benign	0.1294	benign	-0.355	Destabilizing	0.742	D	0.455	neutral	None	None	None	None	N
T/L	0.066	likely_benign	0.064	benign	-0.382	Destabilizing	0.742	D	0.431	neutral	None	None	None	None	N
T/M	0.0726	likely_benign	0.0747	benign	0.019	Stabilizing	0.984	D	0.509	neutral	None	None	None	None	N
T/N	0.0836	likely_benign	0.0857	benign	-0.094	Destabilizing	0.684	D	0.487	neutral	N	0.452717957	None	None	N
T/P	0.071	likely_benign	0.0661	benign	-0.403	Destabilizing	0.003	N	0.164	neutral	N	0.350030732	None	None	N
T/Q	0.1497	likely_benign	0.1504	benign	-0.417	Destabilizing	0.91	D	0.547	neutral	None	None	None	None	N
T/R	0.1298	likely_benign	0.1404	benign	-0.058	Destabilizing	0.91	D	0.538	neutral	None	None	None	None	N
T/S	0.0878	likely_benign	0.088	benign	-0.299	Destabilizing	0.028	N	0.143	neutral	N	0.433958837	None	None	N
T/V	0.081	likely_benign	0.0794	benign	-0.403	Destabilizing	0.742	D	0.355	neutral	None	None	None	None	N
T/W	0.4616	ambiguous	0.4869	ambiguous	-1.064	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	N
T/Y	0.1868	likely_benign	0.1916	benign	-0.794	Destabilizing	0.984	D	0.477	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.