TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6648	20167;20168;20169	chr2:178727636;178727635;178727634	chr2:179592363;179592362;179592361
N2AB	6331	19216;19217;19218	chr2:178727636;178727635;178727634	chr2:179592363;179592362;179592361
N2A	5404	16435;16436;16437	chr2:178727636;178727635;178727634	chr2:179592363;179592362;179592361
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-50
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0692
• 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	None	None	0.939	N	0.612	0.309	0.53974568202	gnomAD-4.0.0	6.90254E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.67051E-05
V/G	rs752299031	-3.252	0.997	N	0.843	0.723	0.928001726772	gnomAD-2.1.1	8.41E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.83E-05	0
V/G	rs752299031	-3.252	0.997	N	0.843	0.723	0.928001726772	gnomAD-4.0.0	1.38051E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80831E-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	0.3711	ambiguous	0.3863	ambiguous	-2.241	Highly Destabilizing	0.939	D	0.612	neutral	N	0.452760816	None	None	N
V/C	0.9127	likely_pathogenic	0.9201	pathogenic	-2.065	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
V/D	0.9882	likely_pathogenic	0.9911	pathogenic	-2.894	Highly Destabilizing	0.997	D	0.855	deleterious	D	0.546106204	None	None	N
V/E	0.9779	likely_pathogenic	0.9811	pathogenic	-2.681	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
V/F	0.6566	likely_pathogenic	0.7079	pathogenic	-1.319	Destabilizing	0.982	D	0.848	deleterious	D	0.545852715	None	None	N
V/G	0.6976	likely_pathogenic	0.7118	pathogenic	-2.771	Highly Destabilizing	0.997	D	0.843	deleterious	N	0.519354669	None	None	N
V/H	0.9917	likely_pathogenic	0.9935	pathogenic	-2.428	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/I	0.0945	likely_benign	0.1027	benign	-0.755	Destabilizing	0.046	N	0.234	neutral	D	0.527195151	None	None	N
V/K	0.9848	likely_pathogenic	0.9876	pathogenic	-1.79	Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
V/L	0.4749	ambiguous	0.5094	ambiguous	-0.755	Destabilizing	0.76	D	0.529	neutral	D	0.526481012	None	None	N
V/M	0.449	ambiguous	0.4828	ambiguous	-0.995	Destabilizing	0.986	D	0.757	deleterious	None	None	None	None	N
V/N	0.969	likely_pathogenic	0.9746	pathogenic	-2.137	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
V/P	0.9898	likely_pathogenic	0.9932	pathogenic	-1.224	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9717	likely_pathogenic	0.9769	pathogenic	-1.997	Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
V/R	0.9704	likely_pathogenic	0.9756	pathogenic	-1.612	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
V/S	0.8053	likely_pathogenic	0.8147	pathogenic	-2.775	Highly Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
V/T	0.6942	likely_pathogenic	0.6939	pathogenic	-2.418	Highly Destabilizing	0.953	D	0.697	prob.neutral	None	None	None	None	N
V/W	0.9938	likely_pathogenic	0.9958	pathogenic	-1.787	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9681	likely_pathogenic	0.9756	pathogenic	-1.464	Destabilizing	0.998	D	0.835	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.