TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22098	66517;66518;66519	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
N2AB	20457	61594;61595;61596	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
N2A	19530	58813;58814;58815	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
N2B	13033	39322;39323;39324	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
Novex-1	13158	39697;39698;39699	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
Novex-2	13225	39898;39899;39900	chr2:178582077;178582076;178582075	chr2:179446804;179446803;179446802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-48
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.7182
• 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
Q/H	None	None	None	N	0.207	0.122	0.12205267543	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86025E-06	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
Q/A	0.1321	likely_benign	0.13	benign	-0.124	Destabilizing	0.031	N	0.301	neutral	None	None	None	None	N
Q/C	0.5878	likely_pathogenic	0.6246	pathogenic	-0.257	Destabilizing	0.864	D	0.189	neutral	None	None	None	None	N
Q/D	0.2947	likely_benign	0.2564	benign	-0.356	Destabilizing	0.072	N	0.245	neutral	None	None	None	None	N
Q/E	0.0929	likely_benign	0.0855	benign	-0.42	Destabilizing	0.012	N	0.217	neutral	N	0.439095298	None	None	N
Q/F	0.6342	likely_pathogenic	0.6524	pathogenic	-0.586	Destabilizing	0.214	N	0.225	neutral	None	None	None	None	N
Q/G	0.1782	likely_benign	0.1733	benign	-0.195	Destabilizing	0.031	N	0.268	neutral	None	None	None	None	N
Q/H	0.1647	likely_benign	0.1784	benign	0.022	Stabilizing	None	N	0.207	neutral	N	0.436788499	None	None	N
Q/I	0.3868	ambiguous	0.4093	ambiguous	-0.034	Destabilizing	0.214	N	0.267	neutral	None	None	None	None	N
Q/K	0.0697	likely_benign	0.0786	benign	-0.149	Destabilizing	None	N	0.157	neutral	N	0.38861055	None	None	N
Q/L	0.1261	likely_benign	0.1247	benign	-0.034	Destabilizing	0.024	N	0.264	neutral	N	0.461049438	None	None	N
Q/M	0.273	likely_benign	0.2791	benign	-0.073	Destabilizing	0.628	D	0.231	neutral	None	None	None	None	N
Q/N	0.1888	likely_benign	0.187	benign	-0.354	Destabilizing	0.038	N	0.247	neutral	None	None	None	None	N
Q/P	0.3025	likely_benign	0.2233	benign	-0.044	Destabilizing	0.106	N	0.287	neutral	N	0.456355695	None	None	N
Q/R	0.0918	likely_benign	0.095	benign	0.072	Stabilizing	0.012	N	0.301	neutral	N	0.435305632	None	None	N
Q/S	0.1547	likely_benign	0.1427	benign	-0.336	Destabilizing	0.016	N	0.261	neutral	None	None	None	None	N
Q/T	0.1261	likely_benign	0.1304	benign	-0.297	Destabilizing	None	N	0.17	neutral	None	None	None	None	N
Q/V	0.2301	likely_benign	0.2219	benign	-0.044	Destabilizing	0.072	N	0.277	neutral	None	None	None	None	N
Q/W	0.6021	likely_pathogenic	0.6114	pathogenic	-0.681	Destabilizing	0.864	D	0.209	neutral	None	None	None	None	N
Q/Y	0.434	ambiguous	0.4292	ambiguous	-0.392	Destabilizing	0.12	N	0.258	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.