TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14508	43747;43748;43749	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
N2AB	12867	38824;38825;38826	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
N2A	11940	36043;36044;36045	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
N2B	5443	16552;16553;16554	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
Novex-1	5568	16927;16928;16929	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
Novex-2	5635	17128;17129;17130	chr2:178632372;178632371;178632370	chr2:179497099;179497098;179497097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-96
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1821
• 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
A/T	None	None	0.896	N	0.511	0.241	0.329282125956	gnomAD-4.0.0	6.90055E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04156E-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
A/C	0.6465	likely_pathogenic	0.6723	pathogenic	-0.915	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
A/D	0.8801	likely_pathogenic	0.8182	pathogenic	-1.363	Destabilizing	0.968	D	0.612	neutral	N	0.517583581	None	None	N
A/E	0.7019	likely_pathogenic	0.6003	pathogenic	-1.378	Destabilizing	0.851	D	0.603	neutral	None	None	None	None	N
A/F	0.7225	likely_pathogenic	0.7061	pathogenic	-1.013	Destabilizing	0.988	D	0.628	neutral	None	None	None	None	N
A/G	0.3489	ambiguous	0.2889	benign	-1.262	Destabilizing	0.896	D	0.507	neutral	N	0.495014961	None	None	N
A/H	0.8594	likely_pathogenic	0.8328	pathogenic	-1.476	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
A/I	0.4467	ambiguous	0.4481	ambiguous	-0.361	Destabilizing	0.851	D	0.515	neutral	None	None	None	None	N
A/K	0.6868	likely_pathogenic	0.6009	pathogenic	-1.326	Destabilizing	0.034	N	0.375	neutral	None	None	None	None	N
A/L	0.414	ambiguous	0.4189	ambiguous	-0.361	Destabilizing	0.702	D	0.538	neutral	None	None	None	None	N
A/M	0.4774	ambiguous	0.4851	ambiguous	-0.274	Destabilizing	0.988	D	0.629	neutral	None	None	None	None	N
A/N	0.8163	likely_pathogenic	0.7688	pathogenic	-1.056	Destabilizing	0.976	D	0.627	neutral	None	None	None	None	N
A/P	0.9642	likely_pathogenic	0.9653	pathogenic	-0.526	Destabilizing	0.984	D	0.635	neutral	N	0.517022115	None	None	N
A/Q	0.6622	likely_pathogenic	0.5979	pathogenic	-1.193	Destabilizing	0.976	D	0.653	neutral	None	None	None	None	N
A/R	0.6016	likely_pathogenic	0.5403	ambiguous	-0.995	Destabilizing	0.952	D	0.633	neutral	None	None	None	None	N
A/S	0.2208	likely_benign	0.1941	benign	-1.407	Destabilizing	0.896	D	0.509	neutral	N	0.503532415	None	None	N
A/T	0.1619	likely_benign	0.1491	benign	-1.329	Destabilizing	0.896	D	0.511	neutral	N	0.479972635	None	None	N
A/V	0.172	likely_benign	0.1716	benign	-0.526	Destabilizing	0.011	N	0.177	neutral	N	0.307009083	None	None	N
A/W	0.9654	likely_pathogenic	0.959	pathogenic	-1.404	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
A/Y	0.8689	likely_pathogenic	0.85	pathogenic	-0.997	Destabilizing	0.996	D	0.626	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.