TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6533	19822;19823;19824	chr2:178728227;178728226;178728225	chr2:179592954;179592953;179592952
N2AB	6216	18871;18872;18873	chr2:178728227;178728226;178728225	chr2:179592954;179592953;179592952
N2A	5289	16090;16091;16092	chr2:178728227;178728226;178728225	chr2:179592954;179592953;179592952
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-49
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.7992
• 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	None	None	0.061	N	0.147	0.198	0.0482279557977	gnomAD-4.0.0	1.59273E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86089E-06	0	0
E/K	rs886042142	None	0.98	N	0.377	0.245	0.241078983079	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs886042142	None	0.98	N	0.377	0.245	0.241078983079	gnomAD-4.0.0	1.85978E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54358E-06	0	0
E/Q	None	None	0.99	N	0.35	0.246	0.15556083564	gnomAD-4.0.0	2.05346E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69921E-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	0.2738	likely_benign	0.239	benign	-0.227	Destabilizing	0.99	D	0.392	neutral	N	0.456426129	None	None	N
E/C	0.9258	likely_pathogenic	0.8991	pathogenic	-0.321	Destabilizing	1.0	D	0.511	neutral	None	None	None	None	N
E/D	0.1151	likely_benign	0.1025	benign	-0.286	Destabilizing	0.061	N	0.147	neutral	N	0.419535598	None	None	N
E/F	0.8742	likely_pathogenic	0.8242	pathogenic	-0.057	Destabilizing	0.999	D	0.432	neutral	None	None	None	None	N
E/G	0.1342	likely_benign	0.1214	benign	-0.403	Destabilizing	0.98	D	0.381	neutral	N	0.463630305	None	None	N
E/H	0.5905	likely_pathogenic	0.5095	ambiguous	0.466	Stabilizing	0.998	D	0.341	neutral	None	None	None	None	N
E/I	0.6844	likely_pathogenic	0.5973	pathogenic	0.199	Stabilizing	0.999	D	0.433	neutral	None	None	None	None	N
E/K	0.1949	likely_benign	0.1538	benign	0.211	Stabilizing	0.98	D	0.377	neutral	N	0.457324729	None	None	N
E/L	0.6248	likely_pathogenic	0.5465	ambiguous	0.199	Stabilizing	0.998	D	0.413	neutral	None	None	None	None	N
E/M	0.7049	likely_pathogenic	0.6391	pathogenic	0.004	Stabilizing	1.0	D	0.424	neutral	None	None	None	None	N
E/N	0.3081	likely_benign	0.2574	benign	-0.106	Destabilizing	0.469	N	0.209	neutral	None	None	None	None	N
E/P	0.6122	likely_pathogenic	0.548	ambiguous	0.076	Stabilizing	0.999	D	0.353	neutral	None	None	None	None	N
E/Q	0.1966	likely_benign	0.1688	benign	-0.054	Destabilizing	0.99	D	0.35	neutral	N	0.456933108	None	None	N
E/R	0.3368	likely_benign	0.2673	benign	0.56	Stabilizing	0.998	D	0.33	neutral	None	None	None	None	N
E/S	0.2653	likely_benign	0.2245	benign	-0.281	Destabilizing	0.985	D	0.365	neutral	None	None	None	None	N
E/T	0.4177	ambiguous	0.3518	ambiguous	-0.129	Destabilizing	0.985	D	0.412	neutral	None	None	None	None	N
E/V	0.4773	ambiguous	0.4001	ambiguous	0.076	Stabilizing	0.999	D	0.379	neutral	N	0.491028478	None	None	N
E/W	0.9386	likely_pathogenic	0.899	pathogenic	0.074	Stabilizing	1.0	D	0.577	neutral	None	None	None	None	N
E/Y	0.7487	likely_pathogenic	0.6739	pathogenic	0.18	Stabilizing	0.999	D	0.407	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.