TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3110	9553;9554;9555	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
N2AB	3110	9553;9554;9555	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
N2A	3110	9553;9554;9555	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
N2B	3064	9415;9416;9417	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
Novex-1	3064	9415;9416;9417	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
Novex-2	3064	9415;9416;9417	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627
Novex-3	3110	9553;9554;9555	chr2:178767902;178767901;178767900	chr2:179632629;179632628;179632627

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-21
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.5252
• 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/D	rs2090779143	None	0.966	N	0.561	0.531	0.720176921917	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/D	rs2090779143	None	0.966	N	0.561	0.531	0.720176921917	gnomAD-4.0.0	2.56156E-06	None	None	None	None	N	None	3.38398E-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
Y/A	0.8601	likely_pathogenic	0.8797	pathogenic	-2.525	Highly Destabilizing	0.915	D	0.545	neutral	None	None	None	None	N
Y/C	0.5418	ambiguous	0.6143	pathogenic	-0.84	Destabilizing	0.997	D	0.567	neutral	N	0.460459436	None	None	N
Y/D	0.7511	likely_pathogenic	0.7635	pathogenic	-1.403	Destabilizing	0.966	D	0.561	neutral	N	0.463291863	None	None	N
Y/E	0.9512	likely_pathogenic	0.955	pathogenic	-1.332	Destabilizing	0.949	D	0.536	neutral	None	None	None	None	N
Y/F	0.1148	likely_benign	0.1414	benign	-1.191	Destabilizing	0.005	N	0.149	neutral	N	0.467379199	None	None	N
Y/G	0.7656	likely_pathogenic	0.7677	pathogenic	-2.84	Highly Destabilizing	0.915	D	0.533	neutral	None	None	None	None	N
Y/H	0.5412	ambiguous	0.6006	pathogenic	-1.316	Destabilizing	0.028	N	0.208	neutral	N	0.478856224	None	None	N
Y/I	0.8871	likely_pathogenic	0.9201	pathogenic	-1.558	Destabilizing	0.728	D	0.509	neutral	None	None	None	None	N
Y/K	0.9488	likely_pathogenic	0.9529	pathogenic	-1.294	Destabilizing	0.949	D	0.539	neutral	None	None	None	None	N
Y/L	0.7923	likely_pathogenic	0.8289	pathogenic	-1.558	Destabilizing	0.728	D	0.475	neutral	None	None	None	None	N
Y/M	0.8402	likely_pathogenic	0.8798	pathogenic	-1.02	Destabilizing	0.974	D	0.515	neutral	None	None	None	None	N
Y/N	0.3871	ambiguous	0.4382	ambiguous	-1.526	Destabilizing	0.934	D	0.556	neutral	N	0.438584275	None	None	N
Y/P	0.9871	likely_pathogenic	0.9838	pathogenic	-1.878	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	N
Y/Q	0.9181	likely_pathogenic	0.9307	pathogenic	-1.514	Destabilizing	0.974	D	0.532	neutral	None	None	None	None	N
Y/R	0.8989	likely_pathogenic	0.9035	pathogenic	-0.767	Destabilizing	0.949	D	0.573	neutral	None	None	None	None	N
Y/S	0.6466	likely_pathogenic	0.6961	pathogenic	-1.987	Destabilizing	0.891	D	0.543	neutral	N	0.470240812	None	None	N
Y/T	0.8407	likely_pathogenic	0.8642	pathogenic	-1.827	Destabilizing	0.974	D	0.537	neutral	None	None	None	None	N
Y/V	0.8104	likely_pathogenic	0.8468	pathogenic	-1.878	Destabilizing	0.842	D	0.499	neutral	None	None	None	None	N
Y/W	0.6646	likely_pathogenic	0.6924	pathogenic	-0.816	Destabilizing	0.991	D	0.507	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.