TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5801	17626;17627;17628	chr2:178731365;178731364;178731363	chr2:179596092;179596091;179596090
N2AB	5484	16675;16676;16677	chr2:178731365;178731364;178731363	chr2:179596092;179596091;179596090
N2A	4557	13894;13895;13896	chr2:178731365;178731364;178731363	chr2:179596092;179596091;179596090
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-41
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1836
• 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
V/I	rs556053351	-0.431	None	N	0.261	0.069	0.224531998449	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
V/I	rs556053351	-0.431	None	N	0.261	0.069	0.224531998449	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
V/I	rs556053351	-0.431	None	N	0.261	0.069	0.224531998449	gnomAD-4.0.0	6.56797E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4702E-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
V/A	0.1858	likely_benign	0.1766	benign	-1.902	Destabilizing	0.012	N	0.389	neutral	N	0.463481163	None	None	N
V/C	0.5568	ambiguous	0.5174	ambiguous	-1.348	Destabilizing	0.864	D	0.595	neutral	None	None	None	None	N
V/D	0.3747	ambiguous	0.3316	benign	-2.562	Highly Destabilizing	0.171	N	0.621	neutral	N	0.483029716	None	None	N
V/E	0.3369	likely_benign	0.3075	benign	-2.313	Highly Destabilizing	0.072	N	0.574	neutral	None	None	None	None	N
V/F	0.0778	likely_benign	0.0708	benign	-1.053	Destabilizing	None	N	0.391	neutral	N	0.452880167	None	None	N
V/G	0.2822	likely_benign	0.2756	benign	-2.454	Highly Destabilizing	0.055	N	0.575	neutral	N	0.464174596	None	None	N
V/H	0.3977	ambiguous	0.3607	ambiguous	-2.337	Highly Destabilizing	0.864	D	0.642	neutral	None	None	None	None	N
V/I	0.0641	likely_benign	0.0609	benign	-0.344	Destabilizing	None	N	0.261	neutral	N	0.407203806	None	None	N
V/K	0.5303	ambiguous	0.4659	ambiguous	-1.374	Destabilizing	0.072	N	0.567	neutral	None	None	None	None	N
V/L	0.1738	likely_benign	0.1566	benign	-0.344	Destabilizing	None	N	0.213	neutral	N	0.452186734	None	None	N
V/M	0.1315	likely_benign	0.1207	benign	-0.495	Destabilizing	0.214	N	0.546	neutral	None	None	None	None	N
V/N	0.2275	likely_benign	0.1955	benign	-1.791	Destabilizing	0.214	N	0.626	neutral	None	None	None	None	N
V/P	0.9745	likely_pathogenic	0.9666	pathogenic	-0.838	Destabilizing	0.356	N	0.589	neutral	None	None	None	None	N
V/Q	0.3057	likely_benign	0.286	benign	-1.562	Destabilizing	0.356	N	0.567	neutral	None	None	None	None	N
V/R	0.4085	ambiguous	0.3454	ambiguous	-1.382	Destabilizing	0.356	N	0.609	neutral	None	None	None	None	N
V/S	0.1487	likely_benign	0.1354	benign	-2.375	Highly Destabilizing	0.003	N	0.579	neutral	None	None	None	None	N
V/T	0.1329	likely_benign	0.119	benign	-1.982	Destabilizing	None	N	0.284	neutral	None	None	None	None	N
V/W	0.6128	likely_pathogenic	0.5668	pathogenic	-1.635	Destabilizing	0.676	D	0.665	neutral	None	None	None	None	N
V/Y	0.2925	likely_benign	0.2669	benign	-1.225	Destabilizing	0.12	N	0.599	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.