TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9721	29386;29387;29388	chr2:178706713;178706712;178706711	chr2:179571440;179571439;179571438
N2AB	9404	28435;28436;28437	chr2:178706713;178706712;178706711	chr2:179571440;179571439;179571438
N2A	8477	25654;25655;25656	chr2:178706713;178706712;178706711	chr2:179571440;179571439;179571438
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-83
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1609
• 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/F	None	None	1.0	None	0.837	0.489	0.892673261969	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.8392	likely_pathogenic	0.6688	pathogenic	-2.185	Highly Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
V/C	0.9879	likely_pathogenic	0.9809	pathogenic	-1.497	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/D	0.9981	likely_pathogenic	0.9924	pathogenic	-2.77	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/E	0.9943	likely_pathogenic	0.9795	pathogenic	-2.513	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/F	0.9338	likely_pathogenic	0.8512	pathogenic	-1.123	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/G	0.9495	likely_pathogenic	0.8469	pathogenic	-2.712	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/H	0.9987	likely_pathogenic	0.9958	pathogenic	-2.447	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/I	0.2151	likely_benign	0.1958	benign	-0.674	Destabilizing	0.997	D	0.533	neutral	None	None	None	None	N
V/K	0.996	likely_pathogenic	0.9871	pathogenic	-1.477	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/L	0.9215	likely_pathogenic	0.8563	pathogenic	-0.674	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	N
V/M	0.9231	likely_pathogenic	0.8439	pathogenic	-0.906	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
V/N	0.9956	likely_pathogenic	0.9856	pathogenic	-1.911	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/P	0.996	likely_pathogenic	0.9857	pathogenic	-1.158	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Q	0.9957	likely_pathogenic	0.9855	pathogenic	-1.666	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/R	0.9913	likely_pathogenic	0.9732	pathogenic	-1.491	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/S	0.9691	likely_pathogenic	0.9139	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/T	0.8645	likely_pathogenic	0.7439	pathogenic	-2.068	Highly Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9958	pathogenic	-1.625	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/Y	0.9941	likely_pathogenic	0.9832	pathogenic	-1.318	Destabilizing	1.0	D	0.838	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.