TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5566	16921;16922;16923	chr2:178732273;178732272;178732271	chr2:179597000;179596999;179596998
N2AB	5249	15970;15971;15972	chr2:178732273;178732272;178732271	chr2:179597000;179596999;179596998
N2A	4322	13189;13190;13191	chr2:178732273;178732272;178732271	chr2:179597000;179596999;179596998
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-39
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.3757
• 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
K/T	None	None	None	N	0.357	0.179	0.300784259202	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
K/A	0.3137	likely_benign	0.3683	ambiguous	-0.658	Destabilizing	0.035	N	0.464	neutral	None	None	None	None	N
K/C	0.6723	likely_pathogenic	0.7398	pathogenic	-0.826	Destabilizing	0.824	D	0.616	neutral	None	None	None	None	N
K/D	0.6269	likely_pathogenic	0.6466	pathogenic	-0.435	Destabilizing	0.081	N	0.47	neutral	None	None	None	None	N
K/E	0.1702	likely_benign	0.1855	benign	-0.346	Destabilizing	None	N	0.319	neutral	N	0.516223222	None	None	N
K/F	0.7023	likely_pathogenic	0.755	pathogenic	-0.551	Destabilizing	0.555	D	0.601	neutral	None	None	None	None	N
K/G	0.4937	ambiguous	0.5482	ambiguous	-0.997	Destabilizing	0.149	N	0.546	neutral	None	None	None	None	N
K/H	0.2523	likely_benign	0.2782	benign	-1.403	Destabilizing	0.38	N	0.571	neutral	None	None	None	None	N
K/I	0.2881	likely_benign	0.3267	benign	0.207	Stabilizing	0.188	N	0.615	neutral	N	0.487431211	None	None	N
K/L	0.3096	likely_benign	0.3627	ambiguous	0.207	Stabilizing	0.081	N	0.547	neutral	None	None	None	None	N
K/M	0.1965	likely_benign	0.2221	benign	0.207	Stabilizing	0.824	D	0.566	neutral	None	None	None	None	N
K/N	0.3811	ambiguous	0.4057	ambiguous	-0.611	Destabilizing	0.117	N	0.439	neutral	N	0.493974897	None	None	N
K/P	0.8183	likely_pathogenic	0.8683	pathogenic	-0.052	Destabilizing	0.555	D	0.589	neutral	None	None	None	None	N
K/Q	0.1256	likely_benign	0.137	benign	-0.79	Destabilizing	0.001	N	0.316	neutral	N	0.494213154	None	None	N
K/R	0.0765	likely_benign	0.0791	benign	-0.65	Destabilizing	None	N	0.333	neutral	N	0.479475775	None	None	N
K/S	0.3715	ambiguous	0.4165	ambiguous	-1.275	Destabilizing	0.007	N	0.343	neutral	None	None	None	None	N
K/T	0.1357	likely_benign	0.151	benign	-0.989	Destabilizing	None	N	0.357	neutral	N	0.483615641	None	None	N
K/V	0.261	likely_benign	0.3023	benign	-0.052	Destabilizing	0.081	N	0.581	neutral	None	None	None	None	N
K/W	0.7249	likely_pathogenic	0.7681	pathogenic	-0.409	Destabilizing	0.935	D	0.635	neutral	None	None	None	None	N
K/Y	0.5847	likely_pathogenic	0.6373	pathogenic	-0.073	Destabilizing	0.555	D	0.595	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.