TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25254	75985;75986;75987	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
N2AB	23613	71062;71063;71064	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
N2A	22686	68281;68282;68283	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
N2B	16189	48790;48791;48792	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
Novex-1	16314	49165;49166;49167	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
Novex-2	16381	49366;49367;49368	chr2:178570372;178570371;178570370	chr2:179435099;179435098;179435097
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: Fn3-71
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.398
• 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/L	None	None	None	N	0.165	0.055	0.317667799068	gnomAD-4.0.0	2.0533E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79915E-06	0	1.65755E-05
V/M	None	None	0.188	N	0.499	0.052	0.453401982733	gnomAD-4.0.0	2.0533E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69873E-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	0.1784	likely_benign	0.1744	benign	-1.101	Destabilizing	0.027	N	0.388	neutral	N	0.487734607	None	None	I
V/C	0.7482	likely_pathogenic	0.7665	pathogenic	-0.709	Destabilizing	0.935	D	0.549	neutral	None	None	None	None	I
V/D	0.6218	likely_pathogenic	0.5892	pathogenic	-1.007	Destabilizing	0.38	N	0.63	neutral	None	None	None	None	I
V/E	0.3724	ambiguous	0.3535	ambiguous	-1.087	Destabilizing	0.317	N	0.625	neutral	N	0.473954447	None	None	I
V/F	0.3011	likely_benign	0.2862	benign	-1.081	Destabilizing	0.235	N	0.568	neutral	None	None	None	None	I
V/G	0.2996	likely_benign	0.29	benign	-1.321	Destabilizing	None	N	0.408	neutral	N	0.510419466	None	None	I
V/H	0.6346	likely_pathogenic	0.634	pathogenic	-0.85	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	I
V/I	0.0787	likely_benign	0.0801	benign	-0.638	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	I
V/K	0.3753	ambiguous	0.3879	ambiguous	-0.987	Destabilizing	0.38	N	0.621	neutral	None	None	None	None	I
V/L	0.1316	likely_benign	0.1313	benign	-0.638	Destabilizing	None	N	0.165	neutral	N	0.461569513	None	None	I
V/M	0.1104	likely_benign	0.1147	benign	-0.413	Destabilizing	0.188	N	0.499	neutral	N	0.469002155	None	None	I
V/N	0.3379	likely_benign	0.3274	benign	-0.67	Destabilizing	0.38	N	0.637	neutral	None	None	None	None	I
V/P	0.468	ambiguous	0.4823	ambiguous	-0.757	Destabilizing	0.555	D	0.633	neutral	None	None	None	None	I
V/Q	0.288	likely_benign	0.2936	benign	-0.94	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	I
V/R	0.3449	ambiguous	0.3579	ambiguous	-0.352	Destabilizing	0.38	N	0.643	neutral	None	None	None	None	I
V/S	0.2646	likely_benign	0.2546	benign	-1.068	Destabilizing	0.081	N	0.581	neutral	None	None	None	None	I
V/T	0.1737	likely_benign	0.1639	benign	-1.053	Destabilizing	0.001	N	0.284	neutral	None	None	None	None	I
V/W	0.8524	likely_pathogenic	0.8511	pathogenic	-1.188	Destabilizing	0.935	D	0.67	neutral	None	None	None	None	I
V/Y	0.6787	likely_pathogenic	0.6666	pathogenic	-0.922	Destabilizing	0.555	D	0.571	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.