TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9036	27331;27332;27333	chr2:178712919;178712918;178712917	chr2:179577646;179577645;179577644
N2AB	8719	26380;26381;26382	chr2:178712919;178712918;178712917	chr2:179577646;179577645;179577644
N2A	7792	23599;23600;23601	chr2:178712919;178712918;178712917	chr2:179577646;179577645;179577644
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-76
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1168
• 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	0.542	0.203	0.518697010188	gnomAD-4.0.0	1.59279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86035E-06	0	0
V/L	rs2076875576	None	0.046	N	0.249	0.123	0.31077124679	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs2076875576	None	0.046	N	0.249	0.123	0.31077124679	gnomAD-4.0.0	6.57039E-06	None	None	None	None	N	None	2.41231E-05	0	None	0	0	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	0.3144	likely_benign	0.3866	ambiguous	-2.042	Highly Destabilizing	0.939	D	0.542	neutral	N	0.510293675	None	None	N
V/C	0.8315	likely_pathogenic	0.8593	pathogenic	-1.542	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
V/D	0.885	likely_pathogenic	0.9498	pathogenic	-2.388	Highly Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
V/E	0.784	likely_pathogenic	0.8773	pathogenic	-2.174	Highly Destabilizing	0.997	D	0.771	deleterious	D	0.534713088	None	None	N
V/F	0.3598	ambiguous	0.4222	ambiguous	-1.271	Destabilizing	0.986	D	0.777	deleterious	None	None	None	None	N
V/G	0.5704	likely_pathogenic	0.6963	pathogenic	-2.572	Highly Destabilizing	0.997	D	0.811	deleterious	N	0.502783766	None	None	N
V/H	0.9076	likely_pathogenic	0.9481	pathogenic	-2.183	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
V/I	0.0791	likely_benign	0.0752	benign	-0.571	Destabilizing	0.046	N	0.245	neutral	N	0.50036747	None	None	N
V/K	0.7878	likely_pathogenic	0.8767	pathogenic	-1.757	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
V/L	0.2896	likely_benign	0.2899	benign	-0.571	Destabilizing	0.046	N	0.249	neutral	N	0.512448546	None	None	N
V/M	0.2141	likely_benign	0.2286	benign	-0.553	Destabilizing	0.986	D	0.67	neutral	None	None	None	None	N
V/N	0.7933	likely_pathogenic	0.8879	pathogenic	-2.032	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
V/P	0.9776	likely_pathogenic	0.9883	pathogenic	-1.034	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
V/Q	0.7764	likely_pathogenic	0.8622	pathogenic	-1.884	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
V/R	0.7289	likely_pathogenic	0.8427	pathogenic	-1.577	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
V/S	0.6184	likely_pathogenic	0.7433	pathogenic	-2.675	Highly Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
V/T	0.4122	ambiguous	0.5043	ambiguous	-2.303	Highly Destabilizing	0.953	D	0.617	neutral	None	None	None	None	N
V/W	0.9437	likely_pathogenic	0.9632	pathogenic	-1.696	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
V/Y	0.799	likely_pathogenic	0.8635	pathogenic	-1.315	Destabilizing	0.998	D	0.751	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.