TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8238	24937;24938;24939	chr2:178718394;178718393;178718392	chr2:179583121;179583120;179583119
N2AB	7921	23986;23987;23988	chr2:178718394;178718393;178718392	chr2:179583121;179583120;179583119
N2A	6994	21205;21206;21207	chr2:178718394;178718393;178718392	chr2:179583121;179583120;179583119
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-67
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.4803
• 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/C	rs202193812	-0.381	0.958	N	0.456	0.261	0.690156929516	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66003E-04
Y/C	rs202193812	-0.381	0.958	N	0.456	0.261	0.690156929516	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs202193812	-0.381	0.958	N	0.456	0.261	0.690156929516	gnomAD-4.0.0	1.23938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69527E-06	0	0
Y/F	rs202193812	None	0.68	N	0.493	0.153	0.483596354421	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99494E-07	0	1.65656E-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	0.2113	likely_benign	0.2226	benign	-1.422	Destabilizing	0.003	N	0.17	neutral	None	None	None	None	N
Y/C	0.1313	likely_benign	0.1306	benign	-0.388	Destabilizing	0.958	D	0.456	neutral	N	0.486516391	None	None	N
Y/D	0.1075	likely_benign	0.1174	benign	0.599	Stabilizing	0.001	N	0.272	neutral	N	0.414365504	None	None	N
Y/E	0.2957	likely_benign	0.3055	benign	0.637	Stabilizing	0.002	N	0.181	neutral	None	None	None	None	N
Y/F	0.1114	likely_benign	0.1131	benign	-0.515	Destabilizing	0.68	D	0.493	neutral	N	0.478974343	None	None	N
Y/G	0.1888	likely_benign	0.2052	benign	-1.677	Destabilizing	0.2	N	0.264	neutral	None	None	None	None	N
Y/H	0.1195	likely_benign	0.1304	benign	-0.17	Destabilizing	0.003	N	0.144	neutral	N	0.497213387	None	None	N
Y/I	0.3748	ambiguous	0.3942	ambiguous	-0.71	Destabilizing	0.582	D	0.525	neutral	None	None	None	None	N
Y/K	0.3048	likely_benign	0.346	ambiguous	-0.388	Destabilizing	0.111	N	0.279	neutral	None	None	None	None	N
Y/L	0.3701	ambiguous	0.389	ambiguous	-0.71	Destabilizing	0.2	N	0.317	neutral	None	None	None	None	N
Y/M	0.4701	ambiguous	0.475	ambiguous	-0.492	Destabilizing	0.968	D	0.463	neutral	None	None	None	None	N
Y/N	0.0738	likely_benign	0.0888	benign	-0.658	Destabilizing	0.178	N	0.322	neutral	N	0.485649599	None	None	N
Y/P	0.7409	likely_pathogenic	0.7489	pathogenic	-0.933	Destabilizing	0.738	D	0.512	neutral	None	None	None	None	N
Y/Q	0.2626	likely_benign	0.2804	benign	-0.575	Destabilizing	0.223	N	0.471	neutral	None	None	None	None	N
Y/R	0.1936	likely_benign	0.2206	benign	-0.027	Destabilizing	0.008	N	0.2	neutral	None	None	None	None	N
Y/S	0.0812	likely_benign	0.0875	benign	-1.228	Destabilizing	0.006	N	0.173	neutral	N	0.372073378	None	None	N
Y/T	0.1847	likely_benign	0.1936	benign	-1.099	Destabilizing	0.008	N	0.181	neutral	None	None	None	None	N
Y/V	0.2578	likely_benign	0.2615	benign	-0.933	Destabilizing	0.365	N	0.339	neutral	None	None	None	None	N
Y/W	0.4738	ambiguous	0.4717	ambiguous	-0.331	Destabilizing	0.968	D	0.488	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.