TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31926	96001;96002;96003	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
N2AB	30285	91078;91079;91080	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
N2A	29358	88297;88298;88299	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
N2B	22861	68806;68807;68808	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
Novex-1	22986	69181;69182;69183	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
Novex-2	23053	69382;69383;69384	chr2:178544453;178544452;178544451	chr2:179409180;179409179;179409178
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-121
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0627
• 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
I/T	None	None	1.0	N	0.803	0.554	0.709726528599	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86053E-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
I/A	0.7647	likely_pathogenic	0.7715	pathogenic	-2.96	Highly Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
I/C	0.8772	likely_pathogenic	0.8696	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9979	pathogenic	-3.398	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
I/E	0.996	likely_pathogenic	0.9945	pathogenic	-3.106	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/F	0.6975	likely_pathogenic	0.6228	pathogenic	-1.833	Destabilizing	1.0	D	0.798	deleterious	D	0.524580842	None	None	N
I/G	0.9833	likely_pathogenic	0.9805	pathogenic	-3.543	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/H	0.9924	likely_pathogenic	0.987	pathogenic	-3.044	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/K	0.9897	likely_pathogenic	0.9837	pathogenic	-2.263	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/L	0.2907	likely_benign	0.2581	benign	-1.221	Destabilizing	0.993	D	0.338	neutral	N	0.461043864	None	None	N
I/M	0.3351	likely_benign	0.3153	benign	-1.707	Destabilizing	1.0	D	0.773	deleterious	N	0.46805433	None	None	N
I/N	0.9768	likely_pathogenic	0.9687	pathogenic	-2.853	Highly Destabilizing	1.0	D	0.881	deleterious	N	0.517647061	None	None	N
I/P	0.9965	likely_pathogenic	0.9951	pathogenic	-1.789	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/Q	0.9896	likely_pathogenic	0.9847	pathogenic	-2.589	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/R	0.9809	likely_pathogenic	0.9677	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/S	0.9298	likely_pathogenic	0.9177	pathogenic	-3.545	Highly Destabilizing	1.0	D	0.839	deleterious	N	0.517140082	None	None	N
I/T	0.8924	likely_pathogenic	0.8864	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.803	deleterious	N	0.490388547	None	None	N
I/V	0.08	likely_benign	0.0803	benign	-1.789	Destabilizing	0.993	D	0.273	neutral	N	0.412543415	None	None	N
I/W	0.9941	likely_pathogenic	0.9903	pathogenic	-2.106	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
I/Y	0.9672	likely_pathogenic	0.9467	pathogenic	-1.934	Destabilizing	1.0	D	0.84	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.