TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14204	42835;42836;42837	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
N2AB	12563	37912;37913;37914	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
N2A	11636	35131;35132;35133	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
N2B	5139	15640;15641;15642	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
Novex-1	5264	16015;16016;16017	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
Novex-2	5331	16216;16217;16218	chr2:178633889;178633888;178633887	chr2:179498616;179498615;179498614
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-92
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.2304
• 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
T/P	None	None	1.0	D	0.759	0.543	0.583209036909	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
T/A	0.1847	likely_benign	0.1872	benign	-0.79	Destabilizing	0.999	D	0.524	neutral	N	0.510700209	None	None	N
T/C	0.6283	likely_pathogenic	0.6396	pathogenic	-0.461	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/D	0.66	likely_pathogenic	0.6749	pathogenic	-0.168	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
T/E	0.5887	likely_pathogenic	0.6045	pathogenic	-0.193	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/F	0.5185	ambiguous	0.5225	ambiguous	-0.999	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
T/G	0.3773	ambiguous	0.3782	ambiguous	-1.014	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/H	0.427	ambiguous	0.4538	ambiguous	-1.33	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/I	0.5565	ambiguous	0.5436	ambiguous	-0.293	Destabilizing	1.0	D	0.766	deleterious	D	0.588728255	None	None	N
T/K	0.2438	likely_benign	0.2917	benign	-0.693	Destabilizing	1.0	D	0.765	deleterious	N	0.50418069	None	None	N
T/L	0.2284	likely_benign	0.2164	benign	-0.293	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
T/M	0.1647	likely_benign	0.1566	benign	0.071	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/N	0.2142	likely_benign	0.222	benign	-0.581	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/P	0.5968	likely_pathogenic	0.5654	pathogenic	-0.428	Destabilizing	1.0	D	0.759	deleterious	D	0.588869207	None	None	N
T/Q	0.3281	likely_benign	0.3628	ambiguous	-0.802	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/R	0.2419	likely_benign	0.275	benign	-0.419	Destabilizing	1.0	D	0.78	deleterious	N	0.509887104	None	None	N
T/S	0.1576	likely_benign	0.1577	benign	-0.861	Destabilizing	0.999	D	0.517	neutral	N	0.485866674	None	None	N
T/V	0.4057	ambiguous	0.4118	ambiguous	-0.428	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
T/W	0.8689	likely_pathogenic	0.8763	pathogenic	-0.918	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/Y	0.5817	likely_pathogenic	0.6075	pathogenic	-0.685	Destabilizing	1.0	D	0.789	deleterious	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.