TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22582	67969;67970;67971	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
N2AB	20941	63046;63047;63048	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
N2A	20014	60265;60266;60267	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
N2B	13517	40774;40775;40776	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
Novex-1	13642	41149;41150;41151	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
Novex-2	13709	41350;41351;41352	chr2:178579286;178579285;178579284	chr2:179444013;179444012;179444011
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-127
• Domain position: 23
• Structural Position: 46
• Q(SASA): 0.3684
• Predicted PPI site: I

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	None	None	0.034	D	0.376	0.464	0.529661991002	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.3309	likely_benign	0.2834	benign	-1.542	Destabilizing	0.034	N	0.376	neutral	D	0.578783885	None	None	I
V/C	0.7719	likely_pathogenic	0.7615	pathogenic	-1.327	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	I
V/D	0.9529	likely_pathogenic	0.9296	pathogenic	-0.92	Destabilizing	0.949	D	0.835	deleterious	D	0.608758496	None	None	I
V/E	0.899	likely_pathogenic	0.8572	pathogenic	-0.845	Destabilizing	0.961	D	0.805	deleterious	None	None	None	None	I
V/F	0.4133	ambiguous	0.3721	ambiguous	-1.093	Destabilizing	0.901	D	0.689	prob.neutral	D	0.559257423	None	None	I
V/G	0.6182	likely_pathogenic	0.5588	ambiguous	-1.94	Destabilizing	0.901	D	0.811	deleterious	D	0.608758496	None	None	I
V/H	0.9419	likely_pathogenic	0.9217	pathogenic	-1.538	Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	I
V/I	0.079	likely_benign	0.0805	benign	-0.521	Destabilizing	0.008	N	0.253	neutral	N	0.501435489	None	None	I
V/K	0.9079	likely_pathogenic	0.873	pathogenic	-1.174	Destabilizing	0.961	D	0.806	deleterious	None	None	None	None	I
V/L	0.3615	ambiguous	0.3629	ambiguous	-0.521	Destabilizing	0.156	N	0.597	neutral	D	0.54321842	None	None	I
V/M	0.3043	likely_benign	0.2975	benign	-0.576	Destabilizing	0.923	D	0.599	neutral	None	None	None	None	I
V/N	0.8529	likely_pathogenic	0.8086	pathogenic	-1.102	Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	I
V/P	0.8777	likely_pathogenic	0.8773	pathogenic	-0.826	Destabilizing	0.961	D	0.807	deleterious	None	None	None	None	I
V/Q	0.8542	likely_pathogenic	0.8157	pathogenic	-1.114	Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	I
V/R	0.8651	likely_pathogenic	0.8268	pathogenic	-0.896	Destabilizing	0.961	D	0.835	deleterious	None	None	None	None	I
V/S	0.5905	likely_pathogenic	0.522	ambiguous	-1.794	Destabilizing	0.858	D	0.788	deleterious	None	None	None	None	I
V/T	0.4929	ambiguous	0.4407	ambiguous	-1.577	Destabilizing	0.775	D	0.637	neutral	None	None	None	None	I
V/W	0.9697	likely_pathogenic	0.9628	pathogenic	-1.319	Destabilizing	0.996	D	0.826	deleterious	None	None	None	None	I
V/Y	0.8476	likely_pathogenic	0.8135	pathogenic	-0.98	Destabilizing	0.961	D	0.678	prob.neutral	None	None	None	None	I

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.