TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31388	94387;94388;94389	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
N2AB	29747	89464;89465;89466	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
N2A	28820	86683;86684;86685	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
N2B	22323	67192;67193;67194	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
Novex-1	22448	67567;67568;67569	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
Novex-2	22515	67768;67769;67770	chr2:178547464;178547463;178547462	chr2:179412191;179412190;179412189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-116
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.8828
• Predicted PPI site: I

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/I	None	None	0.998	N	0.596	0.407	0.623091695385	gnomAD-4.0.0	1.59618E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88807E-05	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
R/A	0.8763	likely_pathogenic	0.8201	pathogenic	-0.155	Destabilizing	0.931	D	0.491	neutral	None	None	None	None	I
R/C	0.5254	ambiguous	0.4618	ambiguous	-0.242	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
R/D	0.9656	likely_pathogenic	0.9558	pathogenic	-0.056	Destabilizing	0.996	D	0.549	neutral	None	None	None	None	I
R/E	0.8847	likely_pathogenic	0.8407	pathogenic	0.028	Stabilizing	0.97	D	0.445	neutral	None	None	None	None	I
R/F	0.9382	likely_pathogenic	0.918	pathogenic	-0.337	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I
R/G	0.8484	likely_pathogenic	0.7935	pathogenic	-0.375	Destabilizing	0.98	D	0.572	neutral	N	0.496348517	None	None	I
R/H	0.3453	ambiguous	0.2993	benign	-1.025	Destabilizing	0.999	D	0.445	neutral	None	None	None	None	I
R/I	0.6931	likely_pathogenic	0.6139	pathogenic	0.397	Stabilizing	0.998	D	0.596	neutral	N	0.465705897	None	None	I
R/K	0.2723	likely_benign	0.2353	benign	-0.169	Destabilizing	0.122	N	0.201	neutral	N	0.397344676	None	None	I
R/L	0.6956	likely_pathogenic	0.6069	pathogenic	0.397	Stabilizing	0.985	D	0.572	neutral	None	None	None	None	I
R/M	0.7631	likely_pathogenic	0.694	pathogenic	-0.055	Destabilizing	1.0	D	0.533	neutral	None	None	None	None	I
R/N	0.9332	likely_pathogenic	0.9092	pathogenic	0.067	Stabilizing	0.985	D	0.467	neutral	None	None	None	None	I
R/P	0.8899	likely_pathogenic	0.8519	pathogenic	0.234	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	I
R/Q	0.3194	likely_benign	0.2697	benign	-0.008	Destabilizing	0.97	D	0.492	neutral	None	None	None	None	I
R/S	0.9159	likely_pathogenic	0.8912	pathogenic	-0.331	Destabilizing	0.961	D	0.552	neutral	N	0.446714704	None	None	I
R/T	0.8045	likely_pathogenic	0.7389	pathogenic	-0.096	Destabilizing	0.98	D	0.565	neutral	N	0.487945251	None	None	I
R/V	0.7981	likely_pathogenic	0.7319	pathogenic	0.234	Stabilizing	0.996	D	0.556	neutral	None	None	None	None	I
R/W	0.6111	likely_pathogenic	0.5696	pathogenic	-0.354	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
R/Y	0.8041	likely_pathogenic	0.7688	pathogenic	0.048	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	I

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.