TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9427	28504;28505;28506	chr2:178710818;178710817;178710816	chr2:179575545;179575544;179575543
N2AB	9110	27553;27554;27555	chr2:178710818;178710817;178710816	chr2:179575545;179575544;179575543
N2A	8183	24772;24773;24774	chr2:178710818;178710817;178710816	chr2:179575545;179575544;179575543
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-80
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6333
• Predicted PPI site: I

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	rs1207669528	0.351	0.968	None	0.581	0.23	0.126345400529	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1207669528	0.351	0.968	None	0.581	0.23	0.126345400529	gnomAD-4.0.0	6.84161E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99425E-07	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	0.3949	ambiguous	0.4496	ambiguous	-0.009	Destabilizing	0.851	D	0.628	neutral	None	None	None	None	I
K/C	0.8239	likely_pathogenic	0.8838	pathogenic	-0.496	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
K/D	0.648	likely_pathogenic	0.6954	pathogenic	0.088	Stabilizing	0.976	D	0.634	neutral	None	None	None	None	I
K/E	0.2298	likely_benign	0.2381	benign	0.119	Stabilizing	0.896	D	0.579	neutral	None	None	None	None	I
K/F	0.7862	likely_pathogenic	0.8533	pathogenic	-0.154	Destabilizing	0.988	D	0.732	prob.delet.	None	None	None	None	I
K/G	0.5713	likely_pathogenic	0.6524	pathogenic	-0.219	Destabilizing	0.919	D	0.627	neutral	None	None	None	None	I
K/H	0.2745	likely_benign	0.3459	ambiguous	-0.348	Destabilizing	0.997	D	0.667	neutral	None	None	None	None	I
K/I	0.3956	ambiguous	0.4538	ambiguous	0.469	Stabilizing	0.976	D	0.732	prob.delet.	None	None	None	None	I
K/L	0.4177	ambiguous	0.4821	ambiguous	0.469	Stabilizing	0.851	D	0.628	neutral	None	None	None	None	I
K/M	0.2841	likely_benign	0.3217	benign	0.035	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/N	0.45	ambiguous	0.4997	ambiguous	-0.077	Destabilizing	0.968	D	0.581	neutral	None	None	None	None	I
K/P	0.8863	likely_pathogenic	0.9378	pathogenic	0.337	Stabilizing	0.988	D	0.682	prob.neutral	None	None	None	None	I
K/Q	0.1403	likely_benign	0.1582	benign	-0.162	Destabilizing	0.968	D	0.603	neutral	None	None	None	None	I
K/R	0.0831	likely_benign	0.091	benign	-0.106	Destabilizing	0.059	N	0.258	neutral	None	None	None	None	I
K/S	0.4156	ambiguous	0.4689	ambiguous	-0.547	Destabilizing	0.851	D	0.569	neutral	None	None	None	None	I
K/T	0.159	likely_benign	0.1749	benign	-0.358	Destabilizing	0.103	N	0.294	neutral	None	None	None	None	I
K/V	0.3716	ambiguous	0.4204	ambiguous	0.337	Stabilizing	0.851	D	0.62	neutral	None	None	None	None	I
K/W	0.7774	likely_pathogenic	0.8432	pathogenic	-0.196	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
K/Y	0.6739	likely_pathogenic	0.7609	pathogenic	0.159	Stabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	I

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.