TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22526	67801;67802;67803	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
N2AB	20885	62878;62879;62880	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
N2A	19958	60097;60098;60099	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
N2B	13461	40606;40607;40608	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
Novex-1	13586	40981;40982;40983	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
Novex-2	13653	41182;41183;41184	chr2:178579621;178579620;178579619	chr2:179444348;179444347;179444346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-51
• Domain position: 76
• Structural Position: 111
• Q(SASA): 0.3817
• 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/D	rs751993220	-1.3	0.425	N	0.401	0.081	0.21279746466	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.15935E-04	None	0	0	None	0	None	0	0	0
E/D	rs751993220	-1.3	0.425	N	0.401	0.081	0.21279746466	gnomAD-4.0.0	6.36831E-06	None	None	None	None	N	None	0	9.14704E-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
E/A	0.1661	likely_benign	0.1836	benign	-1.2	Destabilizing	0.425	N	0.301	neutral	N	0.465857825	None	None	N
E/C	0.7036	likely_pathogenic	0.6919	pathogenic	-0.784	Destabilizing	0.995	D	0.549	neutral	None	None	None	None	N
E/D	0.4604	ambiguous	0.4761	ambiguous	-1.527	Destabilizing	0.425	N	0.401	neutral	N	0.466760429	None	None	N
E/F	0.5964	likely_pathogenic	0.607	pathogenic	-1.136	Destabilizing	0.704	D	0.615	neutral	None	None	None	None	N
E/G	0.2627	likely_benign	0.3118	benign	-1.544	Destabilizing	0.642	D	0.497	neutral	N	0.501722625	None	None	N
E/H	0.4985	ambiguous	0.5115	ambiguous	-1.282	Destabilizing	0.944	D	0.536	neutral	None	None	None	None	N
E/I	0.1669	likely_benign	0.189	benign	-0.253	Destabilizing	0.013	N	0.407	neutral	None	None	None	None	N
E/K	0.1182	likely_benign	0.1355	benign	-0.925	Destabilizing	0.27	N	0.409	neutral	N	0.459009211	None	None	N
E/L	0.2563	likely_benign	0.2856	benign	-0.253	Destabilizing	0.001	N	0.377	neutral	None	None	None	None	N
E/M	0.2698	likely_benign	0.2974	benign	0.289	Stabilizing	0.893	D	0.578	neutral	None	None	None	None	N
E/N	0.4841	ambiguous	0.5266	ambiguous	-1.207	Destabilizing	0.704	D	0.475	neutral	None	None	None	None	N
E/P	0.9801	likely_pathogenic	0.9802	pathogenic	-0.55	Destabilizing	0.828	D	0.579	neutral	None	None	None	None	N
E/Q	0.1003	likely_benign	0.1084	benign	-1.107	Destabilizing	0.01	N	0.133	neutral	N	0.467647337	None	None	N
E/R	0.194	likely_benign	0.2136	benign	-0.8	Destabilizing	0.543	D	0.431	neutral	None	None	None	None	N
E/S	0.2638	likely_benign	0.2856	benign	-1.695	Destabilizing	0.495	N	0.401	neutral	None	None	None	None	N
E/T	0.1927	likely_benign	0.2115	benign	-1.383	Destabilizing	0.495	N	0.443	neutral	None	None	None	None	N
E/V	0.1122	likely_benign	0.1207	benign	-0.55	Destabilizing	0.139	N	0.297	neutral	N	0.380425423	None	None	N
E/W	0.8449	likely_pathogenic	0.8537	pathogenic	-1.064	Destabilizing	0.995	D	0.573	neutral	None	None	None	None	N
E/Y	0.5889	likely_pathogenic	0.6023	pathogenic	-0.883	Destabilizing	0.981	D	0.613	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.