TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8677	26254;26255;26256	chr2:178715157;178715156;178715155	chr2:179579884;179579883;179579882
N2AB	8360	25303;25304;25305	chr2:178715157;178715156;178715155	chr2:179579884;179579883;179579882
N2A	7433	22522;22523;22524	chr2:178715157;178715156;178715155	chr2:179579884;179579883;179579882
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-72
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2936
• 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	rs778578388	-1.006	0.56	N	0.523	0.226	0.426318900417	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
Y/C	rs778578388	-1.006	0.56	N	0.523	0.226	0.426318900417	gnomAD-4.0.0	4.51598E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93684E-05	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	0.33	likely_benign	0.4407	ambiguous	-2.52	Highly Destabilizing	0.007	N	0.347	neutral	None	None	None	None	N
Y/C	0.1089	likely_benign	0.1207	benign	-0.958	Destabilizing	0.56	D	0.523	neutral	N	0.468457679	None	None	N
Y/D	0.327	likely_benign	0.431	ambiguous	-0.986	Destabilizing	0.055	N	0.517	neutral	N	0.479560495	None	None	N
Y/E	0.3049	likely_benign	0.4571	ambiguous	-0.893	Destabilizing	0.016	N	0.415	neutral	None	None	None	None	N
Y/F	0.083	likely_benign	0.0733	benign	-1.054	Destabilizing	None	N	0.125	neutral	N	0.390964917	None	None	N
Y/G	0.3465	ambiguous	0.4532	ambiguous	-2.84	Highly Destabilizing	0.031	N	0.429	neutral	None	None	None	None	N
Y/H	0.0722	likely_benign	0.09	benign	-1.111	Destabilizing	None	N	0.139	neutral	N	0.486552811	None	None	N
Y/I	0.23	likely_benign	0.2708	benign	-1.537	Destabilizing	0.038	N	0.514	neutral	None	None	None	None	N
Y/K	0.2431	likely_benign	0.3785	ambiguous	-1.096	Destabilizing	0.016	N	0.417	neutral	None	None	None	None	N
Y/L	0.1782	likely_benign	0.2548	benign	-1.537	Destabilizing	0.016	N	0.411	neutral	None	None	None	None	N
Y/M	0.2899	likely_benign	0.3573	ambiguous	-1.145	Destabilizing	0.356	N	0.509	neutral	None	None	None	None	N
Y/N	0.1162	likely_benign	0.1505	benign	-1.311	Destabilizing	0.012	N	0.457	neutral	N	0.454872874	None	None	N
Y/P	0.9541	likely_pathogenic	0.9763	pathogenic	-1.862	Destabilizing	0.136	N	0.58	neutral	None	None	None	None	N
Y/Q	0.1227	likely_benign	0.2055	benign	-1.303	Destabilizing	0.001	N	0.204	neutral	None	None	None	None	N
Y/R	0.1624	likely_benign	0.2609	benign	-0.585	Destabilizing	0.001	N	0.267	neutral	None	None	None	None	N
Y/S	0.1526	likely_benign	0.2033	benign	-1.927	Destabilizing	0.001	N	0.255	neutral	N	0.456499262	None	None	N
Y/T	0.217	likely_benign	0.3044	benign	-1.746	Destabilizing	0.016	N	0.429	neutral	None	None	None	None	N
Y/V	0.1968	likely_benign	0.229	benign	-1.862	Destabilizing	0.031	N	0.422	neutral	None	None	None	None	N
Y/W	0.2825	likely_benign	0.3243	benign	-0.508	Destabilizing	0.628	D	0.463	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.