TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31258	93997;93998;93999	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
N2AB	29617	89074;89075;89076	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
N2A	28690	86293;86294;86295	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
N2B	22193	66802;66803;66804	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
Novex-1	22318	67177;67178;67179	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
Novex-2	22385	67378;67379;67380	chr2:178547854;178547853;178547852	chr2:179412581;179412580;179412579
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-151
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.4154
• 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	rs994627256	None	0.201	N	0.416	0.277	0.36256342048	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85788E-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	0.1478	likely_benign	0.1432	benign	-0.249	Destabilizing	0.334	N	0.469	neutral	N	0.495271947	None	None	N
E/C	0.8665	likely_pathogenic	0.8895	pathogenic	-0.078	Destabilizing	0.982	D	0.621	neutral	None	None	None	None	N
E/D	0.1777	likely_benign	0.1805	benign	-0.337	Destabilizing	0.002	N	0.265	neutral	N	0.516167294	None	None	N
E/F	0.8516	likely_pathogenic	0.8627	pathogenic	-0.057	Destabilizing	0.982	D	0.619	neutral	None	None	None	None	N
E/G	0.1635	likely_benign	0.1804	benign	-0.442	Destabilizing	0.334	N	0.492	neutral	D	0.52584557	None	None	N
E/H	0.5922	likely_pathogenic	0.6157	pathogenic	0.288	Stabilizing	0.947	D	0.502	neutral	None	None	None	None	N
E/I	0.4596	ambiguous	0.4475	ambiguous	0.224	Stabilizing	0.826	D	0.645	neutral	None	None	None	None	N
E/K	0.2115	likely_benign	0.2003	benign	0.481	Stabilizing	0.201	N	0.416	neutral	N	0.491088061	None	None	N
E/L	0.4774	ambiguous	0.4707	ambiguous	0.224	Stabilizing	0.826	D	0.629	neutral	None	None	None	None	N
E/M	0.5018	ambiguous	0.494	ambiguous	0.18	Stabilizing	0.982	D	0.563	neutral	None	None	None	None	N
E/N	0.2924	likely_benign	0.3015	benign	0.011	Stabilizing	0.539	D	0.456	neutral	None	None	None	None	N
E/P	0.3491	ambiguous	0.3218	benign	0.087	Stabilizing	0.826	D	0.574	neutral	None	None	None	None	N
E/Q	0.161	likely_benign	0.1581	benign	0.072	Stabilizing	0.043	N	0.233	neutral	N	0.490154129	None	None	N
E/R	0.3488	ambiguous	0.3464	ambiguous	0.7	Stabilizing	0.7	D	0.499	neutral	None	None	None	None	N
E/S	0.2482	likely_benign	0.2562	benign	-0.096	Destabilizing	0.25	N	0.422	neutral	None	None	None	None	N
E/T	0.2657	likely_benign	0.269	benign	0.073	Stabilizing	0.7	D	0.515	neutral	None	None	None	None	N
E/V	0.2481	likely_benign	0.2346	benign	0.087	Stabilizing	0.781	D	0.588	neutral	D	0.535369131	None	None	N
E/W	0.9375	likely_pathogenic	0.9439	pathogenic	0.1	Stabilizing	0.982	D	0.623	neutral	None	None	None	None	N
E/Y	0.7268	likely_pathogenic	0.7432	pathogenic	0.196	Stabilizing	0.935	D	0.584	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.