TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5420	16483;16484;16485	chr2:178732918;178732917;178732916	chr2:179597645;179597644;179597643
N2AB	5103	15532;15533;15534	chr2:178732918;178732917;178732916	chr2:179597645;179597644;179597643
N2A	4176	12751;12752;12753	chr2:178732918;178732917;178732916	chr2:179597645;179597644;179597643
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-37
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.5313
• 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
D/N	rs765827073	-0.15	0.004	N	0.23	0.169	0.286465849087	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
D/N	rs765827073	-0.15	0.004	N	0.23	0.169	0.286465849087	gnomAD-4.0.0	3.18391E-06	None	None	None	None	N	None	0	0	None	0	2.78149E-05	None	0	0	2.85873E-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
D/A	0.155	likely_benign	0.1638	benign	-0.322	Destabilizing	0.201	N	0.367	neutral	N	0.504390076	None	None	N
D/C	0.6045	likely_pathogenic	0.6183	pathogenic	0.038	Stabilizing	0.992	D	0.451	neutral	None	None	None	None	N
D/E	0.1559	likely_benign	0.1632	benign	-0.571	Destabilizing	0.002	N	0.122	neutral	N	0.419424607	None	None	N
D/F	0.5315	ambiguous	0.5645	pathogenic	-0.255	Destabilizing	0.972	D	0.424	neutral	None	None	None	None	N
D/G	0.1341	likely_benign	0.1425	benign	-0.588	Destabilizing	0.004	N	0.163	neutral	N	0.497176102	None	None	N
D/H	0.2402	likely_benign	0.2541	benign	-0.435	Destabilizing	0.896	D	0.384	neutral	N	0.519340885	None	None	N
D/I	0.4002	ambiguous	0.4226	ambiguous	0.346	Stabilizing	0.92	D	0.437	neutral	None	None	None	None	N
D/K	0.3294	likely_benign	0.3638	ambiguous	-0.025	Destabilizing	0.447	N	0.325	neutral	None	None	None	None	N
D/L	0.3361	likely_benign	0.3582	ambiguous	0.346	Stabilizing	0.617	D	0.399	neutral	None	None	None	None	N
D/M	0.5608	ambiguous	0.59	pathogenic	0.691	Stabilizing	0.992	D	0.405	neutral	None	None	None	None	N
D/N	0.0855	likely_benign	0.09	benign	-0.334	Destabilizing	0.004	N	0.23	neutral	N	0.500619052	None	None	N
D/P	0.8402	likely_pathogenic	0.8576	pathogenic	0.148	Stabilizing	0.92	D	0.395	neutral	None	None	None	None	N
D/Q	0.2781	likely_benign	0.2976	benign	-0.262	Destabilizing	0.127	N	0.235	neutral	None	None	None	None	N
D/R	0.3483	ambiguous	0.3766	ambiguous	0.091	Stabilizing	0.617	D	0.397	neutral	None	None	None	None	N
D/S	0.1106	likely_benign	0.1161	benign	-0.481	Destabilizing	0.25	N	0.254	neutral	None	None	None	None	N
D/T	0.2242	likely_benign	0.2422	benign	-0.276	Destabilizing	0.617	D	0.305	neutral	None	None	None	None	N
D/V	0.2448	likely_benign	0.2617	benign	0.148	Stabilizing	0.81	D	0.404	neutral	N	0.483516158	None	None	N
D/W	0.8572	likely_pathogenic	0.8798	pathogenic	-0.159	Destabilizing	0.992	D	0.543	neutral	None	None	None	None	N
D/Y	0.2549	likely_benign	0.2717	benign	-0.039	Destabilizing	0.963	D	0.425	neutral	N	0.500659124	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.