TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19764	59515;59516;59517	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
N2AB	18123	54592;54593;54594	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
N2A	17196	51811;51812;51813	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
N2B	10699	32320;32321;32322	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
Novex-1	10824	32695;32696;32697	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
Novex-2	10891	32896;32897;32898	chr2:178592829;178592828;178592827	chr2:179457556;179457555;179457554
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-31
• Domain position: 85
• Structural Position: 115
• Q(SASA): 0.1916
• 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
G/S	rs1239011047	None	0.041	D	0.488	0.49	0.223146558224	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
G/A	0.7458	likely_pathogenic	0.7496	pathogenic	-0.642	Destabilizing	0.004	N	0.433	neutral	D	0.541806428	None	None	I
G/C	0.8969	likely_pathogenic	0.8944	pathogenic	-0.968	Destabilizing	0.974	D	0.877	deleterious	D	0.565951071	None	None	I
G/D	0.9277	likely_pathogenic	0.9137	pathogenic	-1.039	Destabilizing	0.83	D	0.877	deleterious	D	0.532082737	None	None	I
G/E	0.9377	likely_pathogenic	0.9228	pathogenic	-1.192	Destabilizing	0.866	D	0.88	deleterious	None	None	None	None	I
G/F	0.9862	likely_pathogenic	0.9827	pathogenic	-1.265	Destabilizing	0.98	D	0.887	deleterious	None	None	None	None	I
G/H	0.979	likely_pathogenic	0.975	pathogenic	-0.896	Destabilizing	0.98	D	0.883	deleterious	None	None	None	None	I
G/I	0.9837	likely_pathogenic	0.9791	pathogenic	-0.663	Destabilizing	0.866	D	0.877	deleterious	None	None	None	None	I
G/K	0.967	likely_pathogenic	0.959	pathogenic	-1.149	Destabilizing	0.764	D	0.879	deleterious	None	None	None	None	I
G/L	0.9742	likely_pathogenic	0.9691	pathogenic	-0.663	Destabilizing	0.764	D	0.871	deleterious	None	None	None	None	I
G/M	0.9811	likely_pathogenic	0.976	pathogenic	-0.504	Destabilizing	0.98	D	0.881	deleterious	None	None	None	None	I
G/N	0.9549	likely_pathogenic	0.9478	pathogenic	-0.759	Destabilizing	0.764	D	0.816	deleterious	None	None	None	None	I
G/P	0.9984	likely_pathogenic	0.9977	pathogenic	-0.621	Destabilizing	0.866	D	0.891	deleterious	None	None	None	None	I
G/Q	0.9487	likely_pathogenic	0.938	pathogenic	-1.098	Destabilizing	0.866	D	0.889	deleterious	None	None	None	None	I
G/R	0.9256	likely_pathogenic	0.9063	pathogenic	-0.618	Destabilizing	0.83	D	0.887	deleterious	D	0.546832858	None	None	I
G/S	0.6456	likely_pathogenic	0.6371	pathogenic	-0.916	Destabilizing	0.041	N	0.488	neutral	D	0.541299449	None	None	I
G/T	0.9204	likely_pathogenic	0.9111	pathogenic	-1.011	Destabilizing	0.764	D	0.857	deleterious	None	None	None	None	I
G/V	0.9607	likely_pathogenic	0.9504	pathogenic	-0.621	Destabilizing	0.709	D	0.871	deleterious	N	0.517625787	None	None	I
G/W	0.9742	likely_pathogenic	0.9662	pathogenic	-1.405	Destabilizing	0.993	D	0.853	deleterious	None	None	None	None	I
G/Y	0.9793	likely_pathogenic	0.9754	pathogenic	-1.084	Destabilizing	0.98	D	0.889	deleterious	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.