TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31758	95497;95498;95499	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
N2AB	30117	90574;90575;90576	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
N2A	29190	87793;87794;87795	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
N2B	22693	68302;68303;68304	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
Novex-1	22818	68677;68678;68679	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
Novex-2	22885	68878;68879;68880	chr2:178545964;178545963;178545962	chr2:179410691;179410690;179410689
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-119
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1624
• 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
V/D	None	None	0.999	D	0.805	0.496	0.864996732094	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
V/A	0.2049	likely_benign	0.205	benign	-1.433	Destabilizing	0.978	D	0.477	neutral	N	0.481332738	None	None	I
V/C	0.747	likely_pathogenic	0.7567	pathogenic	-1.023	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
V/D	0.894	likely_pathogenic	0.9024	pathogenic	-1.533	Destabilizing	0.999	D	0.805	deleterious	D	0.536076803	None	None	I
V/E	0.7698	likely_pathogenic	0.7855	pathogenic	-1.416	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
V/F	0.4028	ambiguous	0.4278	ambiguous	-0.878	Destabilizing	0.994	D	0.741	deleterious	N	0.501612586	None	None	I
V/G	0.5091	ambiguous	0.5329	ambiguous	-1.845	Destabilizing	0.997	D	0.765	deleterious	N	0.518226038	None	None	I
V/H	0.9011	likely_pathogenic	0.9073	pathogenic	-1.379	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
V/I	0.0935	likely_benign	0.0951	benign	-0.354	Destabilizing	0.9	D	0.512	neutral	N	0.4707729	None	None	I
V/K	0.8708	likely_pathogenic	0.8793	pathogenic	-1.326	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
V/L	0.2809	likely_benign	0.313	benign	-0.354	Destabilizing	0.9	D	0.385	neutral	N	0.507589804	None	None	I
V/M	0.1808	likely_benign	0.1861	benign	-0.358	Destabilizing	0.84	D	0.344	neutral	None	None	None	None	I
V/N	0.7596	likely_pathogenic	0.7595	pathogenic	-1.452	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
V/P	0.9026	likely_pathogenic	0.9249	pathogenic	-0.681	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
V/Q	0.7233	likely_pathogenic	0.741	pathogenic	-1.428	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
V/R	0.8266	likely_pathogenic	0.8437	pathogenic	-0.987	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	I
V/S	0.4072	ambiguous	0.4119	ambiguous	-1.999	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
V/T	0.2328	likely_benign	0.2239	benign	-1.75	Destabilizing	0.992	D	0.539	neutral	None	None	None	None	I
V/W	0.9491	likely_pathogenic	0.9596	pathogenic	-1.241	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
V/Y	0.8622	likely_pathogenic	0.8716	pathogenic	-0.844	Destabilizing	0.999	D	0.756	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.