TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26730	80413;80414;80415	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
N2AB	25089	75490;75491;75492	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
N2A	24162	72709;72710;72711	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
N2B	17665	53218;53219;53220	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
Novex-1	17790	53593;53594;53595	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
Novex-2	17857	53794;53795;53796	chr2:178565944;178565943;178565942	chr2:179430671;179430670;179430669
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-82
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2553
• 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
Y/F	None	None	0.073	N	0.257	0.161	0.241078983079	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85902E-06	0	0
Y/H	rs768686591	-1.152	0.999	N	0.614	0.528	0.4018988957	gnomAD-4.0.0	1.59161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
Y/A	0.9868	likely_pathogenic	0.9802	pathogenic	-2.618	Highly Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
Y/C	0.8702	likely_pathogenic	0.8272	pathogenic	-1.018	Destabilizing	1.0	D	0.613	neutral	N	0.463919137	None	None	N
Y/D	0.9884	likely_pathogenic	0.9826	pathogenic	-1.347	Destabilizing	1.0	D	0.647	neutral	N	0.47779343	None	None	N
Y/E	0.9984	likely_pathogenic	0.9975	pathogenic	-1.277	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	N
Y/F	0.0896	likely_benign	0.0925	benign	-1.287	Destabilizing	0.073	N	0.257	neutral	N	0.460833221	None	None	N
Y/G	0.9857	likely_pathogenic	0.9789	pathogenic	-2.913	Highly Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
Y/H	0.8755	likely_pathogenic	0.8342	pathogenic	-1.145	Destabilizing	0.999	D	0.614	neutral	N	0.472059439	None	None	N
Y/I	0.9749	likely_pathogenic	0.9661	pathogenic	-1.716	Destabilizing	0.95	D	0.581	neutral	None	None	None	None	N
Y/K	0.998	likely_pathogenic	0.9968	pathogenic	-1.17	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
Y/L	0.9508	likely_pathogenic	0.9373	pathogenic	-1.716	Destabilizing	0.845	D	0.52	neutral	None	None	None	None	N
Y/M	0.976	likely_pathogenic	0.9688	pathogenic	-1.272	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
Y/N	0.9573	likely_pathogenic	0.9392	pathogenic	-1.406	Destabilizing	1.0	D	0.6	neutral	N	0.489403225	None	None	N
Y/P	0.9917	likely_pathogenic	0.9874	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
Y/Q	0.9963	likely_pathogenic	0.9941	pathogenic	-1.463	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
Y/R	0.9928	likely_pathogenic	0.9893	pathogenic	-0.541	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
Y/S	0.9569	likely_pathogenic	0.9386	pathogenic	-1.955	Destabilizing	0.999	D	0.618	neutral	N	0.488642757	None	None	N
Y/T	0.9906	likely_pathogenic	0.9861	pathogenic	-1.799	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
Y/V	0.9588	likely_pathogenic	0.9448	pathogenic	-2.014	Highly Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
Y/W	0.2724	likely_benign	0.2655	benign	-0.779	Destabilizing	1.0	D	0.615	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.