TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19830	59713;59714;59715	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
N2AB	18189	54790;54791;54792	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
N2A	17262	52009;52010;52011	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
N2B	10765	32518;32519;32520	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
Novex-1	10890	32893;32894;32895	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
Novex-2	10957	33094;33095;33096	chr2:178592517;178592516;178592515	chr2:179457244;179457243;179457242
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-119
• Domain position: 41
• Structural Position: 73
• Q(SASA): 0.641
• 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/R	rs764259290	-0.022	0.003	N	0.172	0.077	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	2.06714E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs764259290	-0.022	0.003	N	0.172	0.077	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	N	None	3.37756E-04	0	0	0	0	None	0	0	0	0	4.78011E-04
K/R	rs764259290	-0.022	0.003	N	0.172	0.077	None	gnomAD-4.0.0	2.3068E-05	None	None	None	None	N	None	2.8758E-04	0	None	0	0	None	0	0	0	0	2.84479E-05

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	0.2929	likely_benign	0.3109	benign	-0.119	Destabilizing	0.775	D	0.498	neutral	None	None	None	None	N
K/C	0.7266	likely_pathogenic	0.7472	pathogenic	-0.198	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
K/D	0.4691	ambiguous	0.5132	ambiguous	0.142	Stabilizing	0.923	D	0.403	neutral	None	None	None	None	N
K/E	0.2141	likely_benign	0.2321	benign	0.173	Stabilizing	0.722	D	0.501	neutral	N	0.481912208	None	None	N
K/F	0.7963	likely_pathogenic	0.8093	pathogenic	-0.201	Destabilizing	0.987	D	0.557	neutral	None	None	None	None	N
K/G	0.3499	ambiguous	0.3727	ambiguous	-0.37	Destabilizing	0.775	D	0.454	neutral	None	None	None	None	N
K/H	0.3192	likely_benign	0.3182	benign	-0.741	Destabilizing	0.961	D	0.435	neutral	None	None	None	None	N
K/I	0.4506	ambiguous	0.4842	ambiguous	0.476	Stabilizing	0.949	D	0.553	neutral	N	0.508618807	None	None	N
K/L	0.4048	ambiguous	0.4304	ambiguous	0.476	Stabilizing	0.775	D	0.454	neutral	None	None	None	None	N
K/M	0.2987	likely_benign	0.3186	benign	0.308	Stabilizing	0.996	D	0.445	neutral	None	None	None	None	N
K/N	0.3896	ambiguous	0.4073	ambiguous	0.149	Stabilizing	0.722	D	0.427	neutral	N	0.451589301	None	None	N
K/P	0.6347	likely_pathogenic	0.6724	pathogenic	0.307	Stabilizing	0.961	D	0.437	neutral	None	None	None	None	N
K/Q	0.1678	likely_benign	0.1743	benign	-0.006	Destabilizing	0.722	D	0.475	neutral	N	0.487627459	None	None	N
K/R	0.0816	likely_benign	0.084	benign	-0.189	Destabilizing	0.003	N	0.172	neutral	N	0.376747613	None	None	N
K/S	0.3611	ambiguous	0.3836	ambiguous	-0.395	Destabilizing	0.775	D	0.431	neutral	None	None	None	None	N
K/T	0.1751	likely_benign	0.1861	benign	-0.195	Destabilizing	0.722	D	0.419	neutral	N	0.476351673	None	None	N
K/V	0.3681	ambiguous	0.4083	ambiguous	0.307	Stabilizing	0.923	D	0.454	neutral	None	None	None	None	N
K/W	0.776	likely_pathogenic	0.7973	pathogenic	-0.17	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
K/Y	0.6307	likely_pathogenic	0.6468	pathogenic	0.17	Stabilizing	0.987	D	0.52	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.