TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27840	83743;83744;83745	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
N2AB	26199	78820;78821;78822	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
N2A	25272	76039;76040;76041	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
N2B	18775	56548;56549;56550	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
Novex-1	18900	56923;56924;56925	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
Novex-2	18967	57124;57125;57126	chr2:178562614;178562613;178562612	chr2:179427341;179427340;179427339
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: Fn3-90
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0771
• 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	rs752446232	-2.999	1.0	D	0.623	0.837	0.818476300364	gnomAD-2.1.1	2.04E-05	None	None	None	None	N	None	0	1.47955E-04	None	0	0	None	0	None	0	0	0
V/A	rs752446232	-2.999	1.0	D	0.623	0.837	0.818476300364	gnomAD-4.0.0	9.60344E-06	None	None	None	None	N	None	0	1.39121E-04	None	0	0	None	0	0	0	0	0
V/I	None	None	0.998	D	0.597	0.422	0.708727380244	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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	0.9401	likely_pathogenic	0.9291	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.623	neutral	D	0.565646172	None	None	N
V/C	0.9749	likely_pathogenic	0.9702	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.9993	pathogenic	-3.726	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.652235802	None	None	N
V/E	0.9979	likely_pathogenic	0.9975	pathogenic	-3.424	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/F	0.9426	likely_pathogenic	0.9351	pathogenic	-1.682	Destabilizing	1.0	D	0.801	deleterious	D	0.572229538	None	None	N
V/G	0.9691	likely_pathogenic	0.9625	pathogenic	-3.385	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.652235802	None	None	N
V/H	0.9993	likely_pathogenic	0.9992	pathogenic	-3.073	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/I	0.1061	likely_benign	0.1025	benign	-1.212	Destabilizing	0.998	D	0.597	neutral	D	0.526387075	None	None	N
V/K	0.9984	likely_pathogenic	0.9982	pathogenic	-2.483	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/L	0.7642	likely_pathogenic	0.7326	pathogenic	-1.212	Destabilizing	0.995	D	0.636	neutral	D	0.527356839	None	None	N
V/M	0.8634	likely_pathogenic	0.8371	pathogenic	-1.46	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/N	0.9969	likely_pathogenic	0.9963	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/P	0.9977	likely_pathogenic	0.9974	pathogenic	-1.742	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/Q	0.9976	likely_pathogenic	0.9972	pathogenic	-2.842	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/R	0.9967	likely_pathogenic	0.9964	pathogenic	-2.415	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/S	0.9864	likely_pathogenic	0.9832	pathogenic	-3.622	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.9597	likely_pathogenic	0.9511	pathogenic	-3.182	Highly Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9994	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.996	likely_pathogenic	0.9955	pathogenic	-1.977	Destabilizing	1.0	D	0.809	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.