TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7318	22177;22178;22179	chr2:178723055;178723054;178723053	chr2:179587782;179587781;179587780
N2AB	7001	21226;21227;21228	chr2:178723055;178723054;178723053	chr2:179587782;179587781;179587780
N2A	6074	18445;18446;18447	chr2:178723055;178723054;178723053	chr2:179587782;179587781;179587780
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-57
• Domain position: 89
• Structural Position: 177
• Q(SASA): 0.6597
• 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
S/P	None	None	0.896	N	0.449	0.255	0.148003135375	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
S/A	0.0903	likely_benign	0.0963	benign	-0.331	Destabilizing	0.016	N	0.143	neutral	N	0.46331221	None	None	N
S/C	0.1426	likely_benign	0.1486	benign	-0.327	Destabilizing	0.99	D	0.444	neutral	N	0.464579657	None	None	N
S/D	0.3574	ambiguous	0.3808	ambiguous	0.5	Stabilizing	0.617	D	0.392	neutral	None	None	None	None	N
S/E	0.4129	ambiguous	0.4506	ambiguous	0.418	Stabilizing	0.617	D	0.395	neutral	None	None	None	None	N
S/F	0.1204	likely_benign	0.1306	benign	-0.935	Destabilizing	0.009	N	0.265	neutral	N	0.506135862	None	None	N
S/G	0.1591	likely_benign	0.1638	benign	-0.444	Destabilizing	0.617	D	0.373	neutral	None	None	None	None	N
S/H	0.2607	likely_benign	0.2745	benign	-0.933	Destabilizing	0.992	D	0.436	neutral	None	None	None	None	N
S/I	0.1736	likely_benign	0.1914	benign	-0.168	Destabilizing	0.739	D	0.428	neutral	None	None	None	None	N
S/K	0.5258	ambiguous	0.5506	ambiguous	-0.292	Destabilizing	0.617	D	0.4	neutral	None	None	None	None	N
S/L	0.0984	likely_benign	0.1048	benign	-0.168	Destabilizing	0.447	N	0.367	neutral	None	None	None	None	N
S/M	0.1984	likely_benign	0.2166	benign	-0.056	Destabilizing	0.977	D	0.436	neutral	None	None	None	None	N
S/N	0.1548	likely_benign	0.1704	benign	-0.099	Destabilizing	0.617	D	0.452	neutral	None	None	None	None	N
S/P	0.8065	likely_pathogenic	0.8093	pathogenic	-0.194	Destabilizing	0.896	D	0.449	neutral	N	0.475847057	None	None	N
S/Q	0.4027	ambiguous	0.4352	ambiguous	-0.288	Destabilizing	0.92	D	0.462	neutral	None	None	None	None	N
S/R	0.4436	ambiguous	0.46	ambiguous	-0.178	Destabilizing	0.85	D	0.445	neutral	None	None	None	None	N
S/T	0.0774	likely_benign	0.0806	benign	-0.216	Destabilizing	0.007	N	0.124	neutral	N	0.429019086	None	None	N
S/V	0.1697	likely_benign	0.1882	benign	-0.194	Destabilizing	0.447	N	0.359	neutral	None	None	None	None	N
S/W	0.2632	likely_benign	0.2711	benign	-0.949	Destabilizing	0.992	D	0.501	neutral	None	None	None	None	N
S/Y	0.1131	likely_benign	0.1187	benign	-0.644	Destabilizing	0.681	D	0.459	neutral	N	0.474833099	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.