TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30814	92665;92666;92667	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
N2AB	29173	87742;87743;87744	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
N2A	28246	84961;84962;84963	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
N2B	21749	65470;65471;65472	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
Novex-1	21874	65845;65846;65847	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
Novex-2	21941	66046;66047;66048	chr2:178549186;178549185;178549184	chr2:179413913;179413912;179413911
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: Fn3-112
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.5908
• 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/T	None	None	0.999	N	0.617	0.255	0.199424873507	gnomAD-4.0.0	3.18253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71582E-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	0.497	ambiguous	0.4591	ambiguous	-0.349	Destabilizing	0.997	D	0.643	neutral	None	None	None	None	N
K/C	0.6292	likely_pathogenic	0.6226	pathogenic	-0.454	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/D	0.88	likely_pathogenic	0.8591	pathogenic	0.028	Stabilizing	0.999	D	0.688	prob.delet.	None	None	None	None	N
K/E	0.4727	ambiguous	0.4227	ambiguous	0.1	Stabilizing	0.991	D	0.635	neutral	N	0.473444653	None	None	N
K/F	0.7702	likely_pathogenic	0.7481	pathogenic	-0.164	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/G	0.7158	likely_pathogenic	0.6924	pathogenic	-0.667	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/H	0.3421	ambiguous	0.3232	benign	-0.941	Destabilizing	1.0	D	0.686	prob.delet.	None	None	None	None	N
K/I	0.368	ambiguous	0.3422	ambiguous	0.447	Stabilizing	1.0	D	0.805	deleterious	N	0.489912829	None	None	N
K/L	0.4125	ambiguous	0.3946	ambiguous	0.447	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/M	0.3177	likely_benign	0.299	benign	0.25	Stabilizing	1.0	D	0.691	prob.delet.	None	None	None	None	N
K/N	0.7193	likely_pathogenic	0.6706	pathogenic	-0.214	Destabilizing	0.999	D	0.633	neutral	N	0.468855164	None	None	N
K/P	0.7444	likely_pathogenic	0.7102	pathogenic	0.213	Stabilizing	1.0	D	0.7	prob.delet.	None	None	None	None	N
K/Q	0.1915	likely_benign	0.1779	benign	-0.335	Destabilizing	0.997	D	0.659	prob.neutral	N	0.498380383	None	None	N
K/R	0.0808	likely_benign	0.0821	benign	-0.404	Destabilizing	0.451	N	0.306	neutral	N	0.435273054	None	None	N
K/S	0.6306	likely_pathogenic	0.5895	pathogenic	-0.833	Destabilizing	0.997	D	0.663	prob.neutral	None	None	None	None	N
K/T	0.252	likely_benign	0.2245	benign	-0.573	Destabilizing	0.999	D	0.617	neutral	N	0.420668961	None	None	N
K/V	0.3542	ambiguous	0.3341	benign	0.213	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
K/W	0.7516	likely_pathogenic	0.7421	pathogenic	-0.057	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
K/Y	0.6466	likely_pathogenic	0.6307	pathogenic	0.234	Stabilizing	1.0	D	0.801	deleterious	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.