TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8311	25156;25157;25158	chr2:178718075;178718074;178718073	chr2:179582802;179582801;179582800
N2AB	7994	24205;24206;24207	chr2:178718075;178718074;178718073	chr2:179582802;179582801;179582800
N2A	7067	21424;21425;21426	chr2:178718075;178718074;178718073	chr2:179582802;179582801;179582800
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-68
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.5229
• 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/N	rs749075617	-0.049	0.999	N	0.505	0.304	0.17258766438	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs749075617	-0.049	0.999	N	0.505	0.304	0.17258766438	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	0	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	0.6311	likely_pathogenic	0.6754	pathogenic	-0.293	Destabilizing	0.994	D	0.505	neutral	None	None	None	None	N
K/C	0.8643	likely_pathogenic	0.885	pathogenic	-0.287	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/D	0.7876	likely_pathogenic	0.8261	pathogenic	0.072	Stabilizing	0.999	D	0.517	neutral	None	None	None	None	N
K/E	0.3561	ambiguous	0.3798	ambiguous	0.13	Stabilizing	0.986	D	0.49	neutral	N	0.496176024	None	None	N
K/F	0.9114	likely_pathogenic	0.9282	pathogenic	-0.22	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/G	0.7715	likely_pathogenic	0.8187	pathogenic	-0.601	Destabilizing	0.997	D	0.492	neutral	None	None	None	None	N
K/H	0.3933	ambiguous	0.4142	ambiguous	-1.01	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/I	0.5373	ambiguous	0.5701	pathogenic	0.472	Stabilizing	0.98	D	0.669	neutral	N	0.51838088	None	None	N
K/L	0.6114	likely_pathogenic	0.6532	pathogenic	0.472	Stabilizing	0.95	D	0.496	neutral	None	None	None	None	N
K/M	0.4554	ambiguous	0.4857	ambiguous	0.424	Stabilizing	1.0	D	0.585	neutral	None	None	None	None	N
K/N	0.6707	likely_pathogenic	0.6912	pathogenic	-0.029	Destabilizing	0.999	D	0.505	neutral	N	0.498869613	None	None	N
K/P	0.9659	likely_pathogenic	0.9764	pathogenic	0.248	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/Q	0.1806	likely_benign	0.1897	benign	-0.198	Destabilizing	0.99	D	0.528	neutral	N	0.464295679	None	None	N
K/R	0.0867	likely_benign	0.0877	benign	-0.337	Destabilizing	0.243	N	0.27	neutral	N	0.435666283	None	None	N
K/S	0.6373	likely_pathogenic	0.6679	pathogenic	-0.657	Destabilizing	0.966	D	0.284	neutral	None	None	None	None	N
K/T	0.3108	likely_benign	0.3267	benign	-0.413	Destabilizing	0.973	D	0.513	neutral	N	0.508259887	None	None	N
K/V	0.5072	ambiguous	0.5396	ambiguous	0.248	Stabilizing	0.989	D	0.549	neutral	None	None	None	None	N
K/W	0.8751	likely_pathogenic	0.893	pathogenic	-0.115	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/Y	0.7971	likely_pathogenic	0.826	pathogenic	0.202	Stabilizing	0.997	D	0.644	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.