TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26991	81196;81197;81198	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
N2AB	25350	76273;76274;76275	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
N2A	24423	73492;73493;73494	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
N2B	17926	54001;54002;54003	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
Novex-1	18051	54376;54377;54378	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
Novex-2	18118	54577;54578;54579	chr2:178565161;178565160;178565159	chr2:179429888;179429887;179429886
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: Fn3-84
• Domain position: 20
• Structural Position: 21
• Q(SASA): 0.1311
• 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	rs1362572333	-0.489	0.004	N	0.235	0.098	0.411799315854	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	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	0.235	likely_benign	0.1946	benign	-1.988	Destabilizing	0.201	N	0.369	neutral	N	0.475306815	None	None	N
V/C	0.6869	likely_pathogenic	0.6338	pathogenic	-1.545	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	N
V/D	0.617	likely_pathogenic	0.582	pathogenic	-2.664	Highly Destabilizing	0.379	N	0.572	neutral	N	0.511651617	None	None	N
V/E	0.5007	ambiguous	0.4801	ambiguous	-2.465	Highly Destabilizing	0.617	D	0.528	neutral	None	None	None	None	N
V/F	0.2794	likely_benign	0.2179	benign	-1.181	Destabilizing	0.81	D	0.599	neutral	N	0.511998334	None	None	N
V/G	0.336	likely_benign	0.2877	benign	-2.482	Highly Destabilizing	0.549	D	0.58	neutral	N	0.477182136	None	None	N
V/H	0.6857	likely_pathogenic	0.6156	pathogenic	-2.278	Highly Destabilizing	0.92	D	0.621	neutral	None	None	None	None	N
V/I	0.0897	likely_benign	0.0747	benign	-0.62	Destabilizing	0.004	N	0.235	neutral	N	0.445311982	None	None	N
V/K	0.5836	likely_pathogenic	0.5464	ambiguous	-1.694	Destabilizing	0.617	D	0.533	neutral	None	None	None	None	N
V/L	0.244	likely_benign	0.1827	benign	-0.62	Destabilizing	0.08	N	0.38	neutral	N	0.483136864	None	None	N
V/M	0.1622	likely_benign	0.124	benign	-0.743	Destabilizing	0.85	D	0.578	neutral	None	None	None	None	N
V/N	0.3162	likely_benign	0.253	benign	-1.98	Destabilizing	0.021	N	0.56	neutral	None	None	None	None	N
V/P	0.9609	likely_pathogenic	0.952	pathogenic	-1.049	Destabilizing	0.92	D	0.597	neutral	None	None	None	None	N
V/Q	0.4928	ambiguous	0.4354	ambiguous	-1.85	Destabilizing	0.92	D	0.591	neutral	None	None	None	None	N
V/R	0.5367	ambiguous	0.5104	ambiguous	-1.492	Destabilizing	0.85	D	0.613	neutral	None	None	None	None	N
V/S	0.2127	likely_benign	0.1796	benign	-2.533	Highly Destabilizing	0.059	N	0.48	neutral	None	None	None	None	N
V/T	0.1372	likely_benign	0.124	benign	-2.208	Highly Destabilizing	0.002	N	0.242	neutral	None	None	None	None	N
V/W	0.9091	likely_pathogenic	0.8719	pathogenic	-1.721	Destabilizing	0.992	D	0.651	neutral	None	None	None	None	N
V/Y	0.6748	likely_pathogenic	0.5907	pathogenic	-1.333	Destabilizing	0.92	D	0.593	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.