TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3395	10408;10409;10410	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
N2AB	3395	10408;10409;10410	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
N2A	3395	10408;10409;10410	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
N2B	3349	10270;10271;10272	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
Novex-1	3349	10270;10271;10272	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
Novex-2	3349	10270;10271;10272	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829
Novex-3	3395	10408;10409;10410	chr2:178759104;178759103;178759102	chr2:179623831;179623830;179623829

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-24
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.6984
• 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
F/S	None	None	1.0	N	0.623	0.628	0.788010845958	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.5835	likely_pathogenic	0.6853	pathogenic	-0.641	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	I
F/C	0.7211	likely_pathogenic	0.7148	pathogenic	-0.284	Destabilizing	1.0	D	0.661	neutral	D	0.579444078	None	None	I
F/D	0.7622	likely_pathogenic	0.8011	pathogenic	0.797	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
F/E	0.7756	likely_pathogenic	0.8393	pathogenic	0.756	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
F/G	0.8162	likely_pathogenic	0.8616	pathogenic	-0.782	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
F/H	0.6632	likely_pathogenic	0.7052	pathogenic	0.323	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
F/I	0.3919	ambiguous	0.4492	ambiguous	-0.313	Destabilizing	1.0	D	0.632	neutral	N	0.507134781	None	None	I
F/K	0.8457	likely_pathogenic	0.8958	pathogenic	0.046	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
F/L	0.8954	likely_pathogenic	0.9227	pathogenic	-0.313	Destabilizing	0.999	D	0.528	neutral	N	0.480530439	None	None	I
F/M	0.6231	likely_pathogenic	0.6603	pathogenic	-0.324	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
F/N	0.6655	likely_pathogenic	0.7073	pathogenic	0.062	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
F/P	0.9905	likely_pathogenic	0.9927	pathogenic	-0.403	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
F/Q	0.7718	likely_pathogenic	0.8295	pathogenic	0.035	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
F/R	0.7689	likely_pathogenic	0.8178	pathogenic	0.386	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
F/S	0.4594	ambiguous	0.5532	ambiguous	-0.528	Destabilizing	1.0	D	0.623	neutral	N	0.486340762	None	None	I
F/T	0.5288	ambiguous	0.6229	pathogenic	-0.48	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
F/V	0.369	ambiguous	0.4356	ambiguous	-0.403	Destabilizing	1.0	D	0.587	neutral	N	0.502981042	None	None	I
F/W	0.5669	likely_pathogenic	0.5601	ambiguous	-0.343	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
F/Y	0.2264	likely_benign	0.218	benign	-0.261	Destabilizing	0.999	D	0.512	neutral	N	0.490115808	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.