TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27114	81565;81566;81567	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
N2AB	25473	76642;76643;76644	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
N2A	24546	73861;73862;73863	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
N2B	18049	54370;54371;54372	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
Novex-1	18174	54745;54746;54747	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
Novex-2	18241	54946;54947;54948	chr2:178564792;178564791;178564790	chr2:179429519;179429518;179429517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-85
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4892
• 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/N	None	None	0.967	D	0.474	0.295	0.30212335484	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
K/Q	rs962009573	None	0.967	N	0.507	0.319	0.340992353424	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs962009573	None	0.967	N	0.507	0.319	0.340992353424	gnomAD-4.0.0	4.34183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93662E-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
K/A	0.8033	likely_pathogenic	0.7654	pathogenic	-0.348	Destabilizing	0.916	D	0.521	neutral	None	None	None	None	N
K/C	0.8915	likely_pathogenic	0.8622	pathogenic	-0.319	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/D	0.9503	likely_pathogenic	0.9447	pathogenic	-0.533	Destabilizing	0.987	D	0.531	neutral	None	None	None	None	N
K/E	0.6687	likely_pathogenic	0.6164	pathogenic	-0.464	Destabilizing	0.892	D	0.493	neutral	N	0.515921286	None	None	N
K/F	0.9656	likely_pathogenic	0.9582	pathogenic	-0.21	Destabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
K/G	0.8221	likely_pathogenic	0.8014	pathogenic	-0.688	Destabilizing	0.987	D	0.565	neutral	None	None	None	None	N
K/H	0.6705	likely_pathogenic	0.6209	pathogenic	-1.184	Destabilizing	0.997	D	0.525	neutral	None	None	None	None	N
K/I	0.7621	likely_pathogenic	0.7098	pathogenic	0.516	Stabilizing	0.073	N	0.492	neutral	None	None	None	None	N
K/L	0.7399	likely_pathogenic	0.698	pathogenic	0.516	Stabilizing	0.653	D	0.563	neutral	None	None	None	None	N
K/M	0.6276	likely_pathogenic	0.5548	ambiguous	0.58	Stabilizing	0.991	D	0.522	neutral	N	0.48969053	None	None	N
K/N	0.8585	likely_pathogenic	0.8342	pathogenic	-0.428	Destabilizing	0.967	D	0.474	neutral	D	0.523754123	None	None	N
K/P	0.9305	likely_pathogenic	0.9337	pathogenic	0.258	Stabilizing	0.996	D	0.528	neutral	None	None	None	None	N
K/Q	0.3627	ambiguous	0.3179	benign	-0.586	Destabilizing	0.967	D	0.507	neutral	N	0.474104263	None	None	N
K/R	0.074	likely_benign	0.0717	benign	-0.636	Destabilizing	0.056	N	0.215	neutral	N	0.464956535	None	None	N
K/S	0.8834	likely_pathogenic	0.8567	pathogenic	-0.931	Destabilizing	0.916	D	0.476	neutral	None	None	None	None	N
K/T	0.673	likely_pathogenic	0.5946	pathogenic	-0.68	Destabilizing	0.967	D	0.489	neutral	N	0.516094644	None	None	N
K/V	0.728	likely_pathogenic	0.6753	pathogenic	0.258	Stabilizing	0.653	D	0.575	neutral	None	None	None	None	N
K/W	0.9345	likely_pathogenic	0.9205	pathogenic	-0.156	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/Y	0.9003	likely_pathogenic	0.8809	pathogenic	0.164	Stabilizing	0.987	D	0.662	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.