TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5215	15868;15869;15870	chr2:178733746;178733745;178733744	chr2:179598473;179598472;179598471
N2AB	4898	14917;14918;14919	chr2:178733746;178733745;178733744	chr2:179598473;179598472;179598471
N2A	3971	12136;12137;12138	chr2:178733746;178733745;178733744	chr2:179598473;179598472;179598471
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-35
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3459
• 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/R	None	None	0.012	N	0.191	0.133	0.192905019026	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	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
K/A	0.2255	likely_benign	0.2835	benign	-0.209	Destabilizing	0.688	D	0.329	neutral	None	None	None	None	N
K/C	0.5712	likely_pathogenic	0.6475	pathogenic	-0.403	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
K/D	0.3933	ambiguous	0.4823	ambiguous	0.192	Stabilizing	0.915	D	0.339	neutral	None	None	None	None	N
K/E	0.1068	likely_benign	0.1263	benign	0.263	Stabilizing	0.801	D	0.329	neutral	N	0.510056477	None	None	N
K/F	0.6103	likely_pathogenic	0.6816	pathogenic	-0.077	Destabilizing	0.991	D	0.477	neutral	None	None	None	None	N
K/G	0.3125	likely_benign	0.3944	ambiguous	-0.515	Destabilizing	0.915	D	0.372	neutral	None	None	None	None	N
K/H	0.2058	likely_benign	0.2281	benign	-0.785	Destabilizing	0.974	D	0.411	neutral	None	None	None	None	N
K/I	0.2493	likely_benign	0.295	benign	0.547	Stabilizing	0.934	D	0.452	neutral	N	0.51059588	None	None	N
K/L	0.2562	likely_benign	0.312	benign	0.547	Stabilizing	0.842	D	0.376	neutral	None	None	None	None	N
K/M	0.1729	likely_benign	0.204	benign	0.266	Stabilizing	0.998	D	0.412	neutral	None	None	None	None	N
K/N	0.2476	likely_benign	0.3085	benign	-0.077	Destabilizing	0.801	D	0.321	neutral	N	0.513804987	None	None	N
K/P	0.7664	likely_pathogenic	0.8228	pathogenic	0.326	Stabilizing	0.991	D	0.361	neutral	None	None	None	None	N
K/Q	0.084	likely_benign	0.0921	benign	-0.17	Destabilizing	0.934	D	0.373	neutral	N	0.477458347	None	None	N
K/R	0.0744	likely_benign	0.0745	benign	-0.288	Destabilizing	0.012	N	0.191	neutral	N	0.455722822	None	None	N
K/S	0.221	likely_benign	0.2767	benign	-0.685	Destabilizing	0.728	D	0.291	neutral	None	None	None	None	N
K/T	0.0991	likely_benign	0.1201	benign	-0.424	Destabilizing	0.022	N	0.189	neutral	N	0.467333161	None	None	N
K/V	0.2367	likely_benign	0.287	benign	0.326	Stabilizing	0.842	D	0.403	neutral	None	None	None	None	N
K/W	0.6293	likely_pathogenic	0.6699	pathogenic	-0.004	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	N
K/Y	0.5041	ambiguous	0.562	ambiguous	0.31	Stabilizing	0.991	D	0.457	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.