TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2133	6622;6623;6624	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
N2AB	2133	6622;6623;6624	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
N2A	2133	6622;6623;6624	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
N2B	2087	6484;6485;6486	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
Novex-1	2087	6484;6485;6486	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
Novex-2	2087	6484;6485;6486	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192
Novex-3	2133	6622;6623;6624	chr2:178775467;178775466;178775465	chr2:179640194;179640193;179640192

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-10
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.0707
• 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/I	None	None	0.997	N	0.521	0.272	0.615660705115	gnomAD-4.0.0	1.59071E-06	None	None	None	None	N	None	0	0	None	0	2.77608E-05	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	0.6428	likely_pathogenic	0.7418	pathogenic	-2.146	Highly Destabilizing	0.999	D	0.555	neutral	D	0.536026498	None	None	N
V/C	0.9175	likely_pathogenic	0.9332	pathogenic	-1.597	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
V/D	0.9425	likely_pathogenic	0.9671	pathogenic	-3.032	Highly Destabilizing	1.0	D	0.799	deleterious	D	0.544054325	None	None	N
V/E	0.8098	likely_pathogenic	0.8825	pathogenic	-2.868	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/F	0.5607	ambiguous	0.686	pathogenic	-1.232	Destabilizing	1.0	D	0.799	deleterious	D	0.540691374	None	None	N
V/G	0.814	likely_pathogenic	0.8816	pathogenic	-2.567	Highly Destabilizing	1.0	D	0.764	deleterious	N	0.500841304	None	None	N
V/H	0.9281	likely_pathogenic	0.9576	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/I	0.0927	likely_benign	0.1066	benign	-0.978	Destabilizing	0.997	D	0.521	neutral	N	0.482369794	None	None	N
V/K	0.8915	likely_pathogenic	0.9295	pathogenic	-1.737	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/L	0.5594	ambiguous	0.6848	pathogenic	-0.978	Destabilizing	0.997	D	0.539	neutral	N	0.496373883	None	None	N
V/M	0.4037	ambiguous	0.5214	ambiguous	-1.062	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/N	0.8331	likely_pathogenic	0.8955	pathogenic	-1.967	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.997	pathogenic	-1.345	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/Q	0.809	likely_pathogenic	0.8775	pathogenic	-1.897	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/R	0.8441	likely_pathogenic	0.8926	pathogenic	-1.439	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/S	0.7273	likely_pathogenic	0.8178	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/T	0.4832	ambiguous	0.5796	pathogenic	-2.157	Highly Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
V/W	0.979	likely_pathogenic	0.988	pathogenic	-1.754	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/Y	0.9011	likely_pathogenic	0.9365	pathogenic	-1.461	Destabilizing	1.0	D	0.801	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.