TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18966	57121;57122;57123	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
N2AB	17325	52198;52199;52200	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
N2A	16398	49417;49418;49419	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
N2B	9901	29926;29927;29928	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
Novex-1	10026	30301;30302;30303	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
Novex-2	10093	30502;30503;30504	chr2:178598814;178598813;178598812	chr2:179463541;179463540;179463539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-25
• Domain position: 83
• Structural Position: 111
• Q(SASA): 0.1564
• 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
I/M	rs749403840	-0.761	0.677	N	0.357	0.158	0.630611982783	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/M	rs749403840	-0.761	0.677	N	0.357	0.158	0.630611982783	gnomAD-4.0.0	1.59215E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43328E-05	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
I/A	0.7977	likely_pathogenic	0.7831	pathogenic	-2.384	Highly Destabilizing	0.293	N	0.247	neutral	None	None	None	None	I
I/C	0.884	likely_pathogenic	0.8755	pathogenic	-1.725	Destabilizing	1.0	D	0.514	neutral	None	None	None	None	I
I/D	0.9899	likely_pathogenic	0.9871	pathogenic	-2.505	Highly Destabilizing	0.995	D	0.623	neutral	None	None	None	None	I
I/E	0.8519	likely_pathogenic	0.8378	pathogenic	-2.324	Highly Destabilizing	0.995	D	0.61	neutral	None	None	None	None	I
I/F	0.6138	likely_pathogenic	0.5116	ambiguous	-1.484	Destabilizing	0.994	D	0.492	neutral	N	0.484926376	None	None	I
I/G	0.9757	likely_pathogenic	0.9681	pathogenic	-2.882	Highly Destabilizing	0.969	D	0.595	neutral	None	None	None	None	I
I/H	0.9577	likely_pathogenic	0.9406	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
I/K	0.8729	likely_pathogenic	0.8435	pathogenic	-1.662	Destabilizing	0.995	D	0.605	neutral	None	None	None	None	I
I/L	0.2492	likely_benign	0.2292	benign	-0.971	Destabilizing	0.677	D	0.334	neutral	N	0.464164314	None	None	I
I/M	0.1646	likely_benign	0.1497	benign	-0.97	Destabilizing	0.677	D	0.357	neutral	N	0.498106317	None	None	I
I/N	0.9184	likely_pathogenic	0.9062	pathogenic	-1.891	Destabilizing	0.998	D	0.641	neutral	N	0.470332054	None	None	I
I/P	0.997	likely_pathogenic	0.9961	pathogenic	-1.421	Destabilizing	0.995	D	0.617	neutral	None	None	None	None	I
I/Q	0.8022	likely_pathogenic	0.7672	pathogenic	-1.831	Destabilizing	0.995	D	0.643	neutral	None	None	None	None	I
I/R	0.8639	likely_pathogenic	0.8262	pathogenic	-1.33	Destabilizing	0.995	D	0.619	neutral	None	None	None	None	I
I/S	0.873	likely_pathogenic	0.8518	pathogenic	-2.599	Highly Destabilizing	0.921	D	0.514	neutral	N	0.494796652	None	None	I
I/T	0.7367	likely_pathogenic	0.736	pathogenic	-2.28	Highly Destabilizing	0.959	D	0.465	neutral	N	0.483040864	None	None	I
I/V	0.0941	likely_benign	0.0908	benign	-1.421	Destabilizing	0.116	N	0.141	neutral	N	0.392605286	None	None	I
I/W	0.9725	likely_pathogenic	0.956	pathogenic	-1.82	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
I/Y	0.9313	likely_pathogenic	0.8934	pathogenic	-1.532	Destabilizing	0.999	D	0.521	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.