TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9008	27247;27248;27249	chr2:178713112;178713111;178713110	chr2:179577839;179577838;179577837
N2AB	8691	26296;26297;26298	chr2:178713112;178713111;178713110	chr2:179577839;179577838;179577837
N2A	7764	23515;23516;23517	chr2:178713112;178713111;178713110	chr2:179577839;179577838;179577837
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-75
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3735
• 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
E/K	rs762241119	0.225	0.001	D	0.179	0.144	0.218845423259	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
E/A	0.12	likely_benign	0.1231	benign	-0.727	Destabilizing	0.09	N	0.471	neutral	D	0.528059156	None	None	N
E/C	0.7652	likely_pathogenic	0.7858	pathogenic	-0.281	Destabilizing	0.981	D	0.539	neutral	None	None	None	None	N
E/D	0.1698	likely_benign	0.1917	benign	-0.604	Destabilizing	0.001	N	0.165	neutral	N	0.502547423	None	None	N
E/F	0.5978	likely_pathogenic	0.6256	pathogenic	-0.242	Destabilizing	0.818	D	0.537	neutral	None	None	None	None	N
E/G	0.1622	likely_benign	0.1773	benign	-1.007	Destabilizing	0.324	N	0.52	neutral	N	0.506753688	None	None	N
E/H	0.3009	likely_benign	0.3282	benign	-0.135	Destabilizing	0.69	D	0.549	neutral	None	None	None	None	N
E/I	0.2576	likely_benign	0.2769	benign	0.011	Stabilizing	0.818	D	0.565	neutral	None	None	None	None	N
E/K	0.0727	likely_benign	0.0842	benign	0.061	Stabilizing	0.001	N	0.179	neutral	D	0.524325418	None	None	N
E/L	0.3394	likely_benign	0.3766	ambiguous	0.011	Stabilizing	0.388	N	0.528	neutral	None	None	None	None	N
E/M	0.3239	likely_benign	0.3529	ambiguous	0.225	Stabilizing	0.818	D	0.526	neutral	None	None	None	None	N
E/N	0.2207	likely_benign	0.2652	benign	-0.501	Destabilizing	0.241	N	0.499	neutral	None	None	None	None	N
E/P	0.8689	likely_pathogenic	0.9045	pathogenic	-0.214	Destabilizing	0.818	D	0.581	neutral	None	None	None	None	N
E/Q	0.0936	likely_benign	0.0983	benign	-0.416	Destabilizing	0.006	N	0.286	neutral	N	0.504008861	None	None	N
E/R	0.133	likely_benign	0.145	benign	0.367	Stabilizing	0.002	N	0.295	neutral	None	None	None	None	N
E/S	0.1435	likely_benign	0.1514	benign	-0.692	Destabilizing	0.024	N	0.199	neutral	None	None	None	None	N
E/T	0.1294	likely_benign	0.1421	benign	-0.451	Destabilizing	0.241	N	0.517	neutral	None	None	None	None	N
E/V	0.1627	likely_benign	0.1684	benign	-0.214	Destabilizing	0.324	N	0.551	neutral	N	0.492023785	None	None	N
E/W	0.8267	likely_pathogenic	0.8541	pathogenic	0.066	Stabilizing	0.981	D	0.587	neutral	None	None	None	None	N
E/Y	0.466	ambiguous	0.5135	ambiguous	0.043	Stabilizing	0.818	D	0.55	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.