TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5419	16480;16481;16482	chr2:178732921;178732920;178732919	chr2:179597648;179597647;179597646
N2AB	5102	15529;15530;15531	chr2:178732921;178732920;178732919	chr2:179597648;179597647;179597646
N2A	4175	12748;12749;12750	chr2:178732921;178732920;178732919	chr2:179597648;179597647;179597646
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-37
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1165
• 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	rs1352050140	-2.386	0.334	N	0.501	0.302	0.587751488883	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/A	rs1352050140	-2.386	0.334	N	0.501	0.302	0.587751488883	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85873E-06	0	0
V/I	None	None	0.004	N	0.243	0.126	0.452928561435	gnomAD-4.0.0	2.053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-06	1.15945E-05	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	0.1606	likely_benign	0.1776	benign	-1.861	Destabilizing	0.334	N	0.501	neutral	N	0.464181036	None	None	N
V/C	0.774	likely_pathogenic	0.7739	pathogenic	-1.931	Destabilizing	0.992	D	0.601	neutral	None	None	None	None	N
V/D	0.7778	likely_pathogenic	0.7818	pathogenic	-2.621	Highly Destabilizing	0.972	D	0.677	prob.neutral	None	None	None	None	N
V/E	0.6899	likely_pathogenic	0.7044	pathogenic	-2.565	Highly Destabilizing	0.963	D	0.625	neutral	D	0.522837389	None	None	N
V/F	0.3906	ambiguous	0.4097	ambiguous	-1.45	Destabilizing	0.85	D	0.624	neutral	None	None	None	None	N
V/G	0.2755	likely_benign	0.302	benign	-2.211	Highly Destabilizing	0.896	D	0.657	neutral	D	0.534193694	None	None	N
V/H	0.8849	likely_pathogenic	0.8933	pathogenic	-1.613	Destabilizing	0.992	D	0.637	neutral	None	None	None	None	N
V/I	0.0905	likely_benign	0.0866	benign	-0.951	Destabilizing	0.004	N	0.243	neutral	N	0.508414603	None	None	N
V/K	0.8034	likely_pathogenic	0.8103	pathogenic	-1.571	Destabilizing	0.92	D	0.625	neutral	None	None	None	None	N
V/L	0.1732	likely_benign	0.1838	benign	-0.951	Destabilizing	0.001	N	0.201	neutral	N	0.469090997	None	None	N
V/M	0.1652	likely_benign	0.1813	benign	-1.011	Destabilizing	0.85	D	0.593	neutral	None	None	None	None	N
V/N	0.5642	likely_pathogenic	0.5734	pathogenic	-1.674	Destabilizing	0.972	D	0.669	neutral	None	None	None	None	N
V/P	0.6272	likely_pathogenic	0.6422	pathogenic	-1.226	Destabilizing	0.972	D	0.64	neutral	None	None	None	None	N
V/Q	0.7017	likely_pathogenic	0.7086	pathogenic	-1.844	Destabilizing	0.972	D	0.634	neutral	None	None	None	None	N
V/R	0.7395	likely_pathogenic	0.7484	pathogenic	-1.074	Destabilizing	0.92	D	0.671	neutral	None	None	None	None	N
V/S	0.3344	likely_benign	0.354	ambiguous	-2.198	Highly Destabilizing	0.92	D	0.611	neutral	None	None	None	None	N
V/T	0.175	likely_benign	0.1928	benign	-2.03	Highly Destabilizing	0.617	D	0.555	neutral	None	None	None	None	N
V/W	0.9272	likely_pathogenic	0.9356	pathogenic	-1.674	Destabilizing	0.992	D	0.648	neutral	None	None	None	None	N
V/Y	0.8484	likely_pathogenic	0.8591	pathogenic	-1.373	Destabilizing	0.92	D	0.655	neutral	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.