TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9419	28480;28481;28482	chr2:178710842;178710841;178710840	chr2:179575569;179575568;179575567
N2AB	9102	27529;27530;27531	chr2:178710842;178710841;178710840	chr2:179575569;179575568;179575567
N2A	8175	24748;24749;24750	chr2:178710842;178710841;178710840	chr2:179575569;179575568;179575567
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-80
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3309
• 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
H/Q	rs762212243	-0.398	0.999	None	0.528	0.308	0.199424873507	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Q	rs762212243	-0.398	0.999	None	0.528	0.308	0.199424873507	gnomAD-4.0.0	6.84175E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	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
H/A	0.7324	likely_pathogenic	0.7886	pathogenic	-0.883	Destabilizing	0.293	N	0.355	neutral	None	None	None	None	N
H/C	0.4711	ambiguous	0.5802	pathogenic	-0.299	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	N
H/D	0.6865	likely_pathogenic	0.7398	pathogenic	-0.672	Destabilizing	0.979	D	0.52	neutral	None	None	None	None	N
H/E	0.6795	likely_pathogenic	0.7552	pathogenic	-0.599	Destabilizing	0.984	D	0.424	neutral	None	None	None	None	N
H/F	0.584	likely_pathogenic	0.6723	pathogenic	-0.115	Destabilizing	0.999	D	0.562	neutral	None	None	None	None	N
H/G	0.7969	likely_pathogenic	0.8294	pathogenic	-1.204	Destabilizing	0.039	N	0.348	neutral	None	None	None	None	N
H/I	0.7235	likely_pathogenic	0.7898	pathogenic	-0.01	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	N
H/K	0.465	ambiguous	0.5656	pathogenic	-0.809	Destabilizing	0.984	D	0.507	neutral	None	None	None	None	N
H/L	0.3367	likely_benign	0.3759	ambiguous	-0.01	Destabilizing	0.959	D	0.557	neutral	None	None	None	None	N
H/M	0.8132	likely_pathogenic	0.8617	pathogenic	-0.089	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	N
H/N	0.3456	ambiguous	0.3881	ambiguous	-0.744	Destabilizing	0.979	D	0.48	neutral	None	None	None	None	N
H/P	0.8703	likely_pathogenic	0.8082	pathogenic	-0.281	Destabilizing	0.998	D	0.572	neutral	None	None	None	None	N
H/Q	0.4223	ambiguous	0.4997	ambiguous	-0.569	Destabilizing	0.999	D	0.528	neutral	None	None	None	None	N
H/R	0.158	likely_benign	0.1936	benign	-1.024	Destabilizing	0.994	D	0.499	neutral	None	None	None	None	N
H/S	0.5992	likely_pathogenic	0.6634	pathogenic	-0.862	Destabilizing	0.939	D	0.448	neutral	None	None	None	None	N
H/T	0.6925	likely_pathogenic	0.7584	pathogenic	-0.698	Destabilizing	0.969	D	0.563	neutral	None	None	None	None	N
H/V	0.6463	likely_pathogenic	0.7163	pathogenic	-0.281	Destabilizing	0.969	D	0.572	neutral	None	None	None	None	N
H/W	0.6222	likely_pathogenic	0.7019	pathogenic	0.042	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	N
H/Y	0.2358	likely_benign	0.288	benign	0.307	Stabilizing	0.998	D	0.501	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.