TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24821	74686;74687;74688	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
N2AB	23180	69763;69764;69765	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
N2A	22253	66982;66983;66984	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
N2B	15756	47491;47492;47493	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
Novex-1	15881	47866;47867;47868	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
Novex-2	15948	48067;48068;48069	chr2:178571671;178571670;178571669	chr2:179436398;179436397;179436396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-68
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.2321
• 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	rs1250205827	None	0.999	N	0.52	0.431	0.656083742682	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1250205827	None	0.999	N	0.52	0.431	0.656083742682	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	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	0.5318	ambiguous	0.5284	ambiguous	-1.409	Destabilizing	0.999	D	0.52	neutral	N	0.48413435	None	None	N
V/C	0.8546	likely_pathogenic	0.8519	pathogenic	-1.299	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
V/D	0.9026	likely_pathogenic	0.8901	pathogenic	-1.262	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/E	0.7409	likely_pathogenic	0.724	pathogenic	-1.274	Destabilizing	1.0	D	0.811	deleterious	D	0.525204705	None	None	N
V/F	0.5104	ambiguous	0.4796	ambiguous	-1.283	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/G	0.7056	likely_pathogenic	0.6884	pathogenic	-1.694	Destabilizing	1.0	D	0.811	deleterious	N	0.515369337	None	None	N
V/H	0.9244	likely_pathogenic	0.9175	pathogenic	-1.246	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.075	likely_benign	0.0738	benign	-0.734	Destabilizing	0.998	D	0.478	neutral	None	None	None	None	N
V/K	0.7302	likely_pathogenic	0.7023	pathogenic	-1.023	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/L	0.4751	ambiguous	0.452	ambiguous	-0.734	Destabilizing	0.997	D	0.507	neutral	N	0.479993293	None	None	N
V/M	0.2946	likely_benign	0.2792	benign	-0.687	Destabilizing	1.0	D	0.688	prob.neutral	N	0.503506052	None	None	N
V/N	0.7785	likely_pathogenic	0.7597	pathogenic	-0.871	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/P	0.9282	likely_pathogenic	0.9013	pathogenic	-0.925	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Q	0.7486	likely_pathogenic	0.7297	pathogenic	-1.087	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/R	0.7409	likely_pathogenic	0.7245	pathogenic	-0.575	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/S	0.7065	likely_pathogenic	0.7055	pathogenic	-1.429	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/T	0.5138	ambiguous	0.5142	ambiguous	-1.33	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
V/W	0.9662	likely_pathogenic	0.9594	pathogenic	-1.406	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Y	0.8435	likely_pathogenic	0.8326	pathogenic	-1.082	Destabilizing	1.0	D	0.795	deleterious	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.