TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2221	6886;6887;6888	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
N2AB	2221	6886;6887;6888	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
N2A	2221	6886;6887;6888	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
N2B	2175	6748;6749;6750	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
Novex-1	2175	6748;6749;6750	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
Novex-2	2175	6748;6749;6750	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775
Novex-3	2221	6886;6887;6888	chr2:178775050;178775049;178775048	chr2:179639777;179639776;179639775

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-11
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.6199
• 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	None	None	0.656	N	0.521	0.185	0.28722502521	gnomAD-4.0.0	1.5908E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85683E-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
R/A	0.8412	likely_pathogenic	0.8591	pathogenic	-0.163	Destabilizing	0.754	D	0.589	neutral	None	None	None	None	N
R/C	0.4444	ambiguous	0.4564	ambiguous	0.02	Stabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
R/D	0.9392	likely_pathogenic	0.9479	pathogenic	0.112	Stabilizing	0.956	D	0.627	neutral	None	None	None	None	N
R/E	0.7137	likely_pathogenic	0.7388	pathogenic	0.219	Stabilizing	0.86	D	0.575	neutral	None	None	None	None	N
R/F	0.8359	likely_pathogenic	0.8624	pathogenic	-0.113	Destabilizing	0.978	D	0.707	prob.neutral	None	None	None	None	N
R/G	0.7512	likely_pathogenic	0.7847	pathogenic	-0.445	Destabilizing	0.822	D	0.573	neutral	N	0.50724639	None	None	N
R/H	0.2079	likely_benign	0.2216	benign	-1.032	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
R/I	0.572	likely_pathogenic	0.608	pathogenic	0.573	Stabilizing	0.915	D	0.709	prob.delet.	None	None	None	None	N
R/K	0.2146	likely_benign	0.2267	benign	-0.064	Destabilizing	0.656	D	0.521	neutral	N	0.482878303	None	None	N
R/L	0.5219	ambiguous	0.5465	ambiguous	0.573	Stabilizing	0.754	D	0.575	neutral	None	None	None	None	N
R/M	0.6647	likely_pathogenic	0.7043	pathogenic	0.163	Stabilizing	0.992	D	0.675	prob.neutral	D	0.574403267	None	None	N
R/N	0.8891	likely_pathogenic	0.9026	pathogenic	0.394	Stabilizing	0.956	D	0.607	neutral	None	None	None	None	N
R/P	0.9836	likely_pathogenic	0.9851	pathogenic	0.35	Stabilizing	0.978	D	0.711	prob.delet.	None	None	None	None	N
R/Q	0.2086	likely_benign	0.223	benign	0.273	Stabilizing	0.978	D	0.619	neutral	None	None	None	None	N
R/S	0.8592	likely_pathogenic	0.8752	pathogenic	-0.127	Destabilizing	0.698	D	0.61	neutral	N	0.507771269	None	None	N
R/T	0.6997	likely_pathogenic	0.7264	pathogenic	0.15	Stabilizing	0.014	N	0.357	neutral	N	0.511817793	None	None	N
R/V	0.6743	likely_pathogenic	0.698	pathogenic	0.35	Stabilizing	0.915	D	0.603	neutral	None	None	None	None	N
R/W	0.4192	ambiguous	0.4696	ambiguous	0.013	Stabilizing	0.997	D	0.707	prob.neutral	D	0.656819331	None	None	N
R/Y	0.7372	likely_pathogenic	0.7718	pathogenic	0.369	Stabilizing	0.993	D	0.709	prob.delet.	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.