TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17482	52669;52670;52671	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
N2AB	15841	47746;47747;47748	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
N2A	14914	44965;44966;44967	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
N2B	8417	25474;25475;25476	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
Novex-1	8542	25849;25850;25851	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
Novex-2	8609	26050;26051;26052	chr2:178608439;178608438;178608437	chr2:179473166;179473165;179473164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-15
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3106
• 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/A	rs765605129	-1.27	0.896	N	0.455	0.23	0.536381233585	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.32E-06	0
V/A	rs765605129	-1.27	0.896	N	0.455	0.23	0.536381233585	gnomAD-4.0.0	6.87298E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66406E-05

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	0.3024	likely_benign	0.2664	benign	-1.413	Destabilizing	0.896	D	0.455	neutral	N	0.509536819	None	None	N
V/C	0.759	likely_pathogenic	0.7288	pathogenic	-1.127	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
V/D	0.7051	likely_pathogenic	0.6955	pathogenic	-2.555	Highly Destabilizing	0.984	D	0.673	neutral	N	0.510076191	None	None	N
V/E	0.5888	likely_pathogenic	0.568	pathogenic	-2.558	Highly Destabilizing	0.976	D	0.597	neutral	None	None	None	None	N
V/F	0.3948	ambiguous	0.374	ambiguous	-1.322	Destabilizing	0.968	D	0.541	neutral	N	0.487314355	None	None	N
V/G	0.444	ambiguous	0.3996	ambiguous	-1.715	Destabilizing	0.968	D	0.621	neutral	N	0.502696358	None	None	N
V/H	0.8752	likely_pathogenic	0.8586	pathogenic	-1.491	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
V/I	0.076	likely_benign	0.0751	benign	-0.659	Destabilizing	0.026	N	0.175	neutral	N	0.457278414	None	None	N
V/K	0.7001	likely_pathogenic	0.6783	pathogenic	-1.239	Destabilizing	0.976	D	0.598	neutral	None	None	None	None	N
V/L	0.4363	ambiguous	0.4513	ambiguous	-0.659	Destabilizing	0.64	D	0.395	neutral	N	0.470447413	None	None	N
V/M	0.2676	likely_benign	0.2526	benign	-0.396	Destabilizing	0.976	D	0.467	neutral	None	None	None	None	N
V/N	0.5683	likely_pathogenic	0.5417	ambiguous	-1.226	Destabilizing	0.988	D	0.694	prob.neutral	None	None	None	None	N
V/P	0.6662	likely_pathogenic	0.6723	pathogenic	-0.88	Destabilizing	0.076	N	0.328	neutral	None	None	None	None	N
V/Q	0.6651	likely_pathogenic	0.6313	pathogenic	-1.436	Destabilizing	0.988	D	0.624	neutral	None	None	None	None	N
V/R	0.6382	likely_pathogenic	0.6332	pathogenic	-0.77	Destabilizing	0.988	D	0.688	prob.neutral	None	None	None	None	N
V/S	0.3961	ambiguous	0.3533	ambiguous	-1.54	Destabilizing	0.976	D	0.52	neutral	None	None	None	None	N
V/T	0.2876	likely_benign	0.2478	benign	-1.451	Destabilizing	0.919	D	0.443	neutral	None	None	None	None	N
V/W	0.9471	likely_pathogenic	0.9444	pathogenic	-1.674	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
V/Y	0.7879	likely_pathogenic	0.7796	pathogenic	-1.33	Destabilizing	0.988	D	0.543	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.