TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3906	11941;11942;11943	chr2:178741517;178741516;178741515	chr2:179606244;179606243;179606242
N2AB	3589	10990;10991;10992	chr2:178741517;178741516;178741515	chr2:179606244;179606243;179606242
N2A	None	None	chr2:None	chr2:None
N2B	3543	10852;10853;10854	chr2:178741517;178741516;178741515	chr2:179606244;179606243;179606242
Novex-1	3668	11227;11228;11229	chr2:178741517;178741516;178741515	chr2:179606244;179606243;179606242
Novex-2	3735	11428;11429;11430	chr2:178741517;178741516;178741515	chr2:179606244;179606243;179606242
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: Ig-27
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.598
• 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
Y/C	rs375020177	-0.029	None	N	0.361	0.194	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	1.23998E-04	0	None	0	0	None	0	None	0	0	0
Y/C	rs375020177	-0.029	None	N	0.361	0.194	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs375020177	-0.029	None	N	0.361	0.194	None	gnomAD-4.0.0	4.33767E-06	None	None	None	None	I	None	4.00416E-05	0	None	0	0	None	0	0	0	3.29359E-05	1.60092E-05

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	0.5721	likely_pathogenic	0.4443	ambiguous	-1.988	Destabilizing	0.016	N	0.494	neutral	None	None	None	None	I
Y/C	0.1804	likely_benign	0.1366	benign	-0.559	Destabilizing	None	N	0.361	neutral	N	0.510178058	None	None	I
Y/D	0.3693	ambiguous	0.2711	benign	-0.366	Destabilizing	0.029	N	0.63	neutral	N	0.498895283	None	None	I
Y/E	0.693	likely_pathogenic	0.5709	pathogenic	-0.311	Destabilizing	0.038	N	0.583	neutral	None	None	None	None	I
Y/F	0.1137	likely_benign	0.1019	benign	-0.855	Destabilizing	0.055	N	0.561	neutral	N	0.482561214	None	None	I
Y/G	0.6018	likely_pathogenic	0.4728	ambiguous	-2.279	Highly Destabilizing	0.038	N	0.588	neutral	None	None	None	None	I
Y/H	0.1884	likely_benign	0.1452	benign	-0.697	Destabilizing	None	N	0.161	neutral	N	0.491910118	None	None	I
Y/I	0.5001	ambiguous	0.376	ambiguous	-1.133	Destabilizing	0.002	N	0.257	neutral	None	None	None	None	I
Y/K	0.6131	likely_pathogenic	0.487	ambiguous	-0.81	Destabilizing	0.038	N	0.62	neutral	None	None	None	None	I
Y/L	0.5158	ambiguous	0.3961	ambiguous	-1.133	Destabilizing	0.016	N	0.519	neutral	None	None	None	None	I
Y/M	0.6835	likely_pathogenic	0.577	pathogenic	-0.733	Destabilizing	0.356	N	0.622	neutral	None	None	None	None	I
Y/N	0.207	likely_benign	0.1512	benign	-1.04	Destabilizing	0.029	N	0.626	neutral	N	0.488595349	None	None	I
Y/P	0.9022	likely_pathogenic	0.8291	pathogenic	-1.409	Destabilizing	0.214	N	0.616	neutral	None	None	None	None	I
Y/Q	0.5503	ambiguous	0.4159	ambiguous	-1.013	Destabilizing	0.002	N	0.258	neutral	None	None	None	None	I
Y/R	0.4186	ambiguous	0.3129	benign	-0.328	Destabilizing	0.12	N	0.617	neutral	None	None	None	None	I
Y/S	0.2123	likely_benign	0.1574	benign	-1.568	Destabilizing	None	N	0.356	neutral	N	0.467829584	None	None	I
Y/T	0.4247	ambiguous	0.3163	benign	-1.425	Destabilizing	0.038	N	0.581	neutral	None	None	None	None	I
Y/V	0.4189	ambiguous	0.315	benign	-1.409	Destabilizing	0.038	N	0.549	neutral	None	None	None	None	I
Y/W	0.4684	ambiguous	0.4275	ambiguous	-0.533	Destabilizing	0.864	D	0.601	neutral	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.