TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6986	21181;21182;21183	chr2:178724419;178724418;178724417	chr2:179589146;179589145;179589144
N2AB	6669	20230;20231;20232	chr2:178724419;178724418;178724417	chr2:179589146;179589145;179589144
N2A	5742	17449;17450;17451	chr2:178724419;178724418;178724417	chr2:179589146;179589145;179589144
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-54
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.6246
• 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	rs779709860	0.158	0.994	N	0.433	0.319	0.26547132957	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65948E-04
K/N	rs779709860	0.158	0.994	N	0.433	0.319	0.26547132957	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs779709860	0.158	0.994	N	0.433	0.319	0.26547132957	gnomAD-4.0.0	6.84348E-07	None	None	None	None	N	None	0	2.23754E-05	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	0.2725	likely_benign	0.2476	benign	-0.027	Destabilizing	0.97	D	0.478	neutral	None	None	None	None	N
K/C	0.5739	likely_pathogenic	0.5198	ambiguous	-0.36	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	N
K/D	0.4206	ambiguous	0.3871	ambiguous	0.047	Stabilizing	0.942	D	0.445	neutral	None	None	None	None	N
K/E	0.1147	likely_benign	0.1058	benign	0.075	Stabilizing	0.248	N	0.291	neutral	N	0.450152946	None	None	N
K/F	0.5222	ambiguous	0.4573	ambiguous	-0.157	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	N
K/G	0.4259	ambiguous	0.379	ambiguous	-0.242	Destabilizing	0.985	D	0.459	neutral	None	None	None	None	N
K/H	0.2012	likely_benign	0.1862	benign	-0.406	Destabilizing	1.0	D	0.487	neutral	None	None	None	None	N
K/I	0.1716	likely_benign	0.1542	benign	0.466	Stabilizing	0.983	D	0.537	neutral	None	None	None	None	N
K/L	0.2218	likely_benign	0.1983	benign	0.466	Stabilizing	0.942	D	0.474	neutral	None	None	None	None	N
K/M	0.1364	likely_benign	0.1256	benign	0.083	Stabilizing	0.998	D	0.487	neutral	N	0.515417933	None	None	N
K/N	0.2085	likely_benign	0.1907	benign	0.021	Stabilizing	0.994	D	0.433	neutral	N	0.494618586	None	None	N
K/P	0.9273	likely_pathogenic	0.9204	pathogenic	0.33	Stabilizing	0.999	D	0.485	neutral	None	None	None	None	N
K/Q	0.0895	likely_benign	0.0854	benign	-0.081	Destabilizing	0.989	D	0.445	neutral	N	0.465063683	None	None	N
K/R	0.0792	likely_benign	0.0769	benign	-0.113	Destabilizing	0.961	D	0.439	neutral	N	0.464103678	None	None	N
K/S	0.2839	likely_benign	0.2497	benign	-0.445	Destabilizing	0.97	D	0.446	neutral	None	None	None	None	N
K/T	0.1292	likely_benign	0.1241	benign	-0.262	Destabilizing	0.961	D	0.444	neutral	N	0.492559716	None	None	N
K/V	0.1745	likely_benign	0.1537	benign	0.33	Stabilizing	0.503	D	0.352	neutral	None	None	None	None	N
K/W	0.6643	likely_pathogenic	0.6035	pathogenic	-0.198	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/Y	0.4192	ambiguous	0.3686	ambiguous	0.146	Stabilizing	0.999	D	0.563	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.