TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18141	54646;54647;54648	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
N2AB	16500	49723;49724;49725	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
N2A	15573	46942;46943;46944	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
N2B	9076	27451;27452;27453	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
Novex-1	9201	27826;27827;27828	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
Novex-2	9268	28027;28028;28029	chr2:178604266;178604265;178604264	chr2:179468993;179468992;179468991
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-19
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0792
• 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	0.982	D	0.783	0.55	0.826369311445	gnomAD-4.0.0	1.42257E-06	None	None	None	None	N	None	0	2.58318E-05	None	4.34028E-05	0	None	0	0	0	0	0
V/I	rs527461961	None	0.046	N	0.258	0.237	0.51028768548	gnomAD-4.0.0	4.979E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.4659E-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	0.9148	likely_pathogenic	0.877	pathogenic	-2.75	Highly Destabilizing	0.939	D	0.612	neutral	D	0.536843948	None	None	N
V/C	0.9626	likely_pathogenic	0.9525	pathogenic	-2.204	Highly Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9987	pathogenic	-3.579	Highly Destabilizing	0.997	D	0.886	deleterious	D	0.611606988	None	None	N
V/E	0.9963	likely_pathogenic	0.9952	pathogenic	-3.27	Highly Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
V/F	0.9404	likely_pathogenic	0.9161	pathogenic	-1.497	Destabilizing	0.982	D	0.783	deleterious	D	0.554948203	None	None	N
V/G	0.9506	likely_pathogenic	0.9262	pathogenic	-3.316	Highly Destabilizing	0.997	D	0.885	deleterious	D	0.611606988	None	None	N
V/H	0.999	likely_pathogenic	0.9985	pathogenic	-3.039	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
V/I	0.1101	likely_benign	0.0984	benign	-1.077	Destabilizing	0.046	N	0.258	neutral	N	0.492717218	None	None	N
V/K	0.9967	likely_pathogenic	0.9961	pathogenic	-2.259	Highly Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	N
V/L	0.6573	likely_pathogenic	0.6456	pathogenic	-1.077	Destabilizing	0.76	D	0.503	neutral	N	0.497896279	None	None	N
V/M	0.8212	likely_pathogenic	0.7887	pathogenic	-1.427	Destabilizing	0.986	D	0.679	prob.neutral	None	None	None	None	N
V/N	0.9963	likely_pathogenic	0.9946	pathogenic	-2.93	Highly Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
V/P	0.9978	likely_pathogenic	0.997	pathogenic	-1.622	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/Q	0.9951	likely_pathogenic	0.9937	pathogenic	-2.581	Highly Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
V/R	0.9938	likely_pathogenic	0.9922	pathogenic	-2.256	Highly Destabilizing	0.998	D	0.911	deleterious	None	None	None	None	N
V/S	0.9855	likely_pathogenic	0.9758	pathogenic	-3.408	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
V/T	0.9499	likely_pathogenic	0.9333	pathogenic	-2.957	Highly Destabilizing	0.953	D	0.674	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9987	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9948	likely_pathogenic	0.992	pathogenic	-1.823	Destabilizing	0.998	D	0.794	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.