TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7292	22099;22100;22101	chr2:178723133;178723132;178723131	chr2:179587860;179587859;179587858
N2AB	6975	21148;21149;21150	chr2:178723133;178723132;178723131	chr2:179587860;179587859;179587858
N2A	6048	18367;18368;18369	chr2:178723133;178723132;178723131	chr2:179587860;179587859;179587858
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-57
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1167
• 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/N	None	None	0.959	N	0.504	0.351	0.360961692134	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0923	likely_benign	0.0941	benign	-0.302	Destabilizing	0.927	D	0.394	neutral	None	None	None	None	N
S/C	0.1086	likely_benign	0.1099	benign	-0.693	Destabilizing	0.999	D	0.589	neutral	N	0.476088754	None	None	N
S/D	0.8416	likely_pathogenic	0.8132	pathogenic	-1.791	Destabilizing	0.088	N	0.238	neutral	None	None	None	None	N
S/E	0.9195	likely_pathogenic	0.9031	pathogenic	-1.759	Destabilizing	0.864	D	0.505	neutral	None	None	None	None	N
S/F	0.695	likely_pathogenic	0.6519	pathogenic	-0.827	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/G	0.115	likely_benign	0.1325	benign	-0.521	Destabilizing	0.01	N	0.156	neutral	N	0.499290814	None	None	N
S/H	0.8191	likely_pathogenic	0.7766	pathogenic	-1.184	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
S/I	0.2937	likely_benign	0.2998	benign	0.174	Stabilizing	0.998	D	0.643	neutral	N	0.474275026	None	None	N
S/K	0.9762	likely_pathogenic	0.9706	pathogenic	-0.561	Destabilizing	0.939	D	0.51	neutral	None	None	None	None	N
S/L	0.2247	likely_benign	0.2454	benign	0.174	Stabilizing	0.984	D	0.59	neutral	None	None	None	None	N
S/M	0.4441	ambiguous	0.4594	ambiguous	0.472	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
S/N	0.3244	likely_benign	0.308	benign	-1.019	Destabilizing	0.959	D	0.504	neutral	N	0.517395069	None	None	N
S/P	0.6075	likely_pathogenic	0.5405	ambiguous	0.047	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	N
S/Q	0.8977	likely_pathogenic	0.8802	pathogenic	-1.236	Destabilizing	0.991	D	0.61	neutral	None	None	None	None	N
S/R	0.9455	likely_pathogenic	0.9329	pathogenic	-0.446	Destabilizing	0.068	N	0.424	neutral	N	0.517395069	None	None	N
S/T	0.1055	likely_benign	0.1068	benign	-0.711	Destabilizing	0.979	D	0.5	neutral	N	0.498637539	None	None	N
S/V	0.2781	likely_benign	0.2803	benign	0.047	Stabilizing	0.984	D	0.626	neutral	None	None	None	None	N
S/W	0.8389	likely_pathogenic	0.7911	pathogenic	-1.012	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
S/Y	0.646	likely_pathogenic	0.5791	pathogenic	-0.563	Destabilizing	0.999	D	0.633	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.