TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26114	78565;78566;78567	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
N2AB	24473	73642;73643;73644	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
N2A	23546	70861;70862;70863	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
N2B	17049	51370;51371;51372	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
Novex-1	17174	51745;51746;51747	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
Novex-2	17241	51946;51947;51948	chr2:178567792;178567791;178567790	chr2:179432519;179432518;179432517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-78
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6693
• 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
Y/C	None	None	1.0	N	0.687	0.465	0.372087925617	gnomAD-4.0.0	1.59195E-06	None	None	None	None	I	None	0	0	None	0	2.77439E-05	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
Y/A	0.8191	likely_pathogenic	0.7424	pathogenic	-0.89	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	I
Y/C	0.3369	likely_benign	0.2448	benign	0.174	Stabilizing	1.0	D	0.687	prob.neutral	N	0.499507493	None	None	I
Y/D	0.7008	likely_pathogenic	0.5955	pathogenic	0.717	Stabilizing	1.0	D	0.687	prob.neutral	N	0.476348886	None	None	I
Y/E	0.9128	likely_pathogenic	0.857	pathogenic	0.686	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	I
Y/F	0.1404	likely_benign	0.1231	benign	-0.598	Destabilizing	0.999	D	0.525	neutral	N	0.492550489	None	None	I
Y/G	0.6705	likely_pathogenic	0.596	pathogenic	-1.082	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
Y/H	0.3862	ambiguous	0.3192	benign	0.039	Stabilizing	1.0	D	0.697	prob.neutral	N	0.500169895	None	None	I
Y/I	0.8694	likely_pathogenic	0.7948	pathogenic	-0.404	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
Y/K	0.8772	likely_pathogenic	0.8325	pathogenic	0.189	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
Y/L	0.7842	likely_pathogenic	0.72	pathogenic	-0.404	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
Y/M	0.8534	likely_pathogenic	0.7954	pathogenic	-0.057	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
Y/N	0.2911	likely_benign	0.2144	benign	0.089	Stabilizing	1.0	D	0.689	prob.neutral	N	0.475772883	None	None	I
Y/P	0.9899	likely_pathogenic	0.9851	pathogenic	-0.547	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
Y/Q	0.8217	likely_pathogenic	0.7546	pathogenic	0.046	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
Y/R	0.6959	likely_pathogenic	0.6348	pathogenic	0.565	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
Y/S	0.4371	ambiguous	0.3385	benign	-0.368	Destabilizing	1.0	D	0.682	prob.neutral	N	0.494473287	None	None	I
Y/T	0.7622	likely_pathogenic	0.6829	pathogenic	-0.308	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
Y/V	0.7833	likely_pathogenic	0.6907	pathogenic	-0.547	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
Y/W	0.6462	likely_pathogenic	0.6069	pathogenic	-0.678	Destabilizing	1.0	D	0.681	prob.neutral	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.