TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15524	46795;46796;46797	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
N2AB	13883	41872;41873;41874	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
N2A	12956	39091;39092;39093	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
N2B	6459	19600;19601;19602	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
Novex-1	6584	19975;19976;19977	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
Novex-2	6651	20176;20177;20178	chr2:178619747;178619746;178619745	chr2:179484474;179484473;179484472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-107
• Domain position: 45
• Structural Position: 115
• Q(SASA): 0.4125
• 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
K/E	rs548285460	None	0.999	D	0.483	0.707	0.529861178392	gnomAD-4.0.0	1.20033E-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
K/A	0.9242	likely_pathogenic	0.9327	pathogenic	-0.341	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
K/C	0.9495	likely_pathogenic	0.9681	pathogenic	-0.09	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/D	0.9571	likely_pathogenic	0.9645	pathogenic	-0.355	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/E	0.829	likely_pathogenic	0.8507	pathogenic	-0.277	Destabilizing	0.999	D	0.483	neutral	D	0.636164364	None	None	N
K/F	0.9819	likely_pathogenic	0.9855	pathogenic	-0.128	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/G	0.9391	likely_pathogenic	0.9464	pathogenic	-0.692	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/H	0.7034	likely_pathogenic	0.7609	pathogenic	-1.219	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/I	0.8809	likely_pathogenic	0.9056	pathogenic	0.559	Stabilizing	1.0	D	0.663	neutral	D	0.635589905	None	None	N
K/L	0.8808	likely_pathogenic	0.8987	pathogenic	0.559	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/M	0.8355	likely_pathogenic	0.8663	pathogenic	0.604	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
K/N	0.9177	likely_pathogenic	0.9285	pathogenic	-0.233	Destabilizing	1.0	D	0.647	neutral	D	0.595204694	None	None	N
K/P	0.9787	likely_pathogenic	0.9788	pathogenic	0.289	Stabilizing	1.0	D	0.602	neutral	None	None	None	None	N
K/Q	0.5663	likely_pathogenic	0.6342	pathogenic	-0.333	Destabilizing	1.0	D	0.627	neutral	D	0.635589905	None	None	N
K/R	0.1315	likely_benign	0.1489	benign	-0.593	Destabilizing	0.999	D	0.487	neutral	N	0.518973252	None	None	N
K/S	0.931	likely_pathogenic	0.9379	pathogenic	-0.724	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
K/T	0.7608	likely_pathogenic	0.7844	pathogenic	-0.459	Destabilizing	1.0	D	0.641	neutral	D	0.594657441	None	None	N
K/V	0.8674	likely_pathogenic	0.8958	pathogenic	0.289	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	N
K/W	0.9692	likely_pathogenic	0.9761	pathogenic	-0.087	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/Y	0.942	likely_pathogenic	0.9546	pathogenic	0.207	Stabilizing	1.0	D	0.603	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.