TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18974	57145;57146;57147	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
N2AB	17333	52222;52223;52224	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
N2A	16406	49441;49442;49443	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
N2B	9909	29950;29951;29952	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
Novex-1	10034	30325;30326;30327	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
Novex-2	10101	30526;30527;30528	chr2:178598790;178598789;178598788	chr2:179463517;179463516;179463515
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-25
• Domain position: 91
• Structural Position: 120
• Q(SASA): 0.249
• 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
A/V	rs1336627311	-0.322	0.946	N	0.444	0.346	0.257292322809	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
A/V	rs1336627311	-0.322	0.946	N	0.444	0.346	0.257292322809	gnomAD-4.0.0	1.59207E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85992E-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
A/C	0.4075	ambiguous	0.4392	ambiguous	-0.757	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	I
A/D	0.8504	likely_pathogenic	0.821	pathogenic	-1.08	Destabilizing	0.988	D	0.625	neutral	None	None	None	None	I
A/E	0.7001	likely_pathogenic	0.6578	pathogenic	-1.113	Destabilizing	0.896	D	0.553	neutral	N	0.466991189	None	None	I
A/F	0.6249	likely_pathogenic	0.5836	pathogenic	-0.983	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	I
A/G	0.2983	likely_benign	0.277	benign	-1.181	Destabilizing	0.896	D	0.483	neutral	N	0.496967379	None	None	I
A/H	0.7982	likely_pathogenic	0.7583	pathogenic	-1.274	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
A/I	0.4901	ambiguous	0.4375	ambiguous	-0.421	Destabilizing	0.988	D	0.618	neutral	None	None	None	None	I
A/K	0.897	likely_pathogenic	0.8701	pathogenic	-1.161	Destabilizing	0.919	D	0.551	neutral	None	None	None	None	I
A/L	0.4368	ambiguous	0.3585	ambiguous	-0.421	Destabilizing	0.919	D	0.541	neutral	None	None	None	None	I
A/M	0.4572	ambiguous	0.4387	ambiguous	-0.32	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
A/N	0.6949	likely_pathogenic	0.6577	pathogenic	-0.851	Destabilizing	0.988	D	0.695	prob.neutral	None	None	None	None	I
A/P	0.0831	likely_benign	0.075	benign	-0.552	Destabilizing	0.004	N	0.361	neutral	N	0.289595562	None	None	I
A/Q	0.6621	likely_pathogenic	0.6038	pathogenic	-1.025	Destabilizing	0.988	D	0.617	neutral	None	None	None	None	I
A/R	0.8564	likely_pathogenic	0.8168	pathogenic	-0.779	Destabilizing	0.988	D	0.613	neutral	None	None	None	None	I
A/S	0.1597	likely_benign	0.1561	benign	-1.202	Destabilizing	0.896	D	0.507	neutral	N	0.440073946	None	None	I
A/T	0.2902	likely_benign	0.2428	benign	-1.149	Destabilizing	0.896	D	0.447	neutral	N	0.462950806	None	None	I
A/V	0.2533	likely_benign	0.2415	benign	-0.552	Destabilizing	0.946	D	0.444	neutral	N	0.447885353	None	None	I
A/W	0.9385	likely_pathogenic	0.9077	pathogenic	-1.307	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
A/Y	0.7643	likely_pathogenic	0.7152	pathogenic	-0.923	Destabilizing	0.996	D	0.723	prob.delet.	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.