TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7006	21241;21242;21243	chr2:178724359;178724358;178724357	chr2:179589086;179589085;179589084
N2AB	6689	20290;20291;20292	chr2:178724359;178724358;178724357	chr2:179589086;179589085;179589084
N2A	5762	17509;17510;17511	chr2:178724359;178724358;178724357	chr2:179589086;179589085;179589084
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-54
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.4866
• 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
R/K	rs771200026	-1.139	None	N	0.228	0.161	0.18995819373	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29249E-04	0	None	0	0	None	0	None	0	0	0
R/K	rs771200026	-1.139	None	N	0.228	0.161	0.18995819373	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs771200026	-1.139	None	N	0.228	0.161	0.18995819373	gnomAD-4.0.0	5.12608E-06	None	None	None	None	N	None	6.7659E-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
R/A	0.3622	ambiguous	0.3225	benign	-1.214	Destabilizing	0.007	N	0.323	neutral	None	None	None	None	N
R/C	0.2913	likely_benign	0.2932	benign	-1.21	Destabilizing	0.864	D	0.433	neutral	None	None	None	None	N
R/D	0.6827	likely_pathogenic	0.6583	pathogenic	-0.239	Destabilizing	0.016	N	0.359	neutral	None	None	None	None	N
R/E	0.277	likely_benign	0.242	benign	-0.138	Destabilizing	None	N	0.226	neutral	None	None	None	None	N
R/F	0.603	likely_pathogenic	0.5665	pathogenic	-1.246	Destabilizing	0.628	D	0.471	neutral	None	None	None	None	N
R/G	0.3057	likely_benign	0.2863	benign	-1.483	Destabilizing	0.024	N	0.365	neutral	D	0.525480211	None	None	N
R/H	0.1284	likely_benign	0.1224	benign	-1.606	Destabilizing	0.356	N	0.417	neutral	None	None	None	None	N
R/I	0.2156	likely_benign	0.2009	benign	-0.495	Destabilizing	0.136	N	0.494	neutral	None	None	None	None	N
R/K	0.0625	likely_benign	0.0586	benign	-1.147	Destabilizing	None	N	0.228	neutral	N	0.424507927	None	None	N
R/L	0.2407	likely_benign	0.2277	benign	-0.495	Destabilizing	0.031	N	0.382	neutral	None	None	None	None	N
R/M	0.2044	likely_benign	0.1857	benign	-0.643	Destabilizing	0.56	D	0.458	neutral	N	0.481766719	None	None	N
R/N	0.4762	ambiguous	0.4187	ambiguous	-0.517	Destabilizing	0.031	N	0.385	neutral	None	None	None	None	N
R/P	0.9067	likely_pathogenic	0.905	pathogenic	-0.716	Destabilizing	0.136	N	0.475	neutral	None	None	None	None	N
R/Q	0.0965	likely_benign	0.0899	benign	-0.826	Destabilizing	0.016	N	0.393	neutral	None	None	None	None	N
R/S	0.3912	ambiguous	0.3415	ambiguous	-1.438	Destabilizing	0.005	N	0.334	neutral	N	0.432223333	None	None	N
R/T	0.1515	likely_benign	0.1324	benign	-1.169	Destabilizing	0.024	N	0.402	neutral	N	0.395971744	None	None	N
R/V	0.2906	likely_benign	0.2566	benign	-0.716	Destabilizing	0.031	N	0.419	neutral	None	None	None	None	N
R/W	0.2357	likely_benign	0.2313	benign	-0.832	Destabilizing	0.828	D	0.446	neutral	N	0.507067808	None	None	N
R/Y	0.4555	ambiguous	0.4154	ambiguous	-0.54	Destabilizing	0.356	N	0.531	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.