TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5144	15655;15656;15657	chr2:178734394;178734393;178734392	chr2:179599121;179599120;179599119
N2AB	4827	14704;14705;14706	chr2:178734394;178734393;178734392	chr2:179599121;179599120;179599119
N2A	3900	11923;11924;11925	chr2:178734394;178734393;178734392	chr2:179599121;179599120;179599119
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-34
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3815
• 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	rs766612317	-0.207	0.117	D	0.503	0.18	0.295623431141	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/K	rs766612317	-0.207	0.117	D	0.503	0.18	0.295623431141	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs766612317	-0.207	0.117	D	0.503	0.18	0.295623431141	gnomAD-4.0.0	5.88951E-05	None	None	None	None	N	None	1.3349E-05	0	None	0	0	None	0	0	7.97028E-05	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	0.0944	likely_benign	0.1055	benign	-0.925	Destabilizing	0.117	N	0.527	neutral	D	0.609632849	None	None	N
E/C	0.5121	ambiguous	0.5862	pathogenic	-0.519	Destabilizing	0.935	D	0.59	neutral	None	None	None	None	N
E/D	0.0653	likely_benign	0.0681	benign	-0.969	Destabilizing	None	N	0.165	neutral	N	0.513354809	None	None	N
E/F	0.3944	ambiguous	0.4642	ambiguous	-0.374	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
E/G	0.116	likely_benign	0.1349	benign	-1.278	Destabilizing	0.117	N	0.541	neutral	D	0.733874274	None	None	N
E/H	0.2199	likely_benign	0.2526	benign	-0.678	Destabilizing	0.555	D	0.525	neutral	None	None	None	None	N
E/I	0.1402	likely_benign	0.1685	benign	0.038	Stabilizing	0.001	N	0.407	neutral	None	None	None	None	N
E/K	0.1009	likely_benign	0.1063	benign	-0.775	Destabilizing	0.117	N	0.503	neutral	D	0.523636015	None	None	N
E/L	0.167	likely_benign	0.2026	benign	0.038	Stabilizing	0.081	N	0.538	neutral	None	None	None	None	N
E/M	0.231	likely_benign	0.2665	benign	0.475	Stabilizing	0.698	D	0.583	neutral	None	None	None	None	N
E/N	0.089	likely_benign	0.1019	benign	-1.143	Destabilizing	0.081	N	0.501	neutral	None	None	None	None	N
E/P	0.4063	ambiguous	0.4621	ambiguous	-0.263	Destabilizing	0.555	D	0.569	neutral	None	None	None	None	N
E/Q	0.0879	likely_benign	0.0965	benign	-1.004	Destabilizing	0.117	N	0.51	neutral	D	0.577110476	None	None	N
E/R	0.1672	likely_benign	0.1713	benign	-0.478	Destabilizing	0.38	N	0.537	neutral	None	None	None	None	N
E/S	0.0986	likely_benign	0.1084	benign	-1.463	Destabilizing	0.081	N	0.505	neutral	None	None	None	None	N
E/T	0.1148	likely_benign	0.1351	benign	-1.176	Destabilizing	0.149	N	0.535	neutral	None	None	None	None	N
E/V	0.101	likely_benign	0.1121	benign	-0.263	Destabilizing	0.062	N	0.547	neutral	N	0.503359067	None	None	N
E/W	0.6598	likely_pathogenic	0.712	pathogenic	-0.127	Destabilizing	0.935	D	0.604	neutral	None	None	None	None	N
E/Y	0.2667	likely_benign	0.3171	benign	-0.149	Destabilizing	0.791	D	0.602	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.