TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9147	27664;27665;27666	chr2:178712483;178712482;178712481	chr2:179577210;179577209;179577208
N2AB	8830	26713;26714;26715	chr2:178712483;178712482;178712481	chr2:179577210;179577209;179577208
N2A	7903	23932;23933;23934	chr2:178712483;178712482;178712481	chr2:179577210;179577209;179577208
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-77
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2812
• 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
K/E	None	None	0.994	D	0.503	0.542	0.431379191433	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	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
K/A	0.9267	likely_pathogenic	0.9023	pathogenic	-0.922	Destabilizing	0.992	D	0.508	neutral	None	None	None	None	N
K/C	0.8953	likely_pathogenic	0.8724	pathogenic	-0.948	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
K/D	0.981	likely_pathogenic	0.9703	pathogenic	-0.187	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/E	0.7812	likely_pathogenic	0.7085	pathogenic	-0.051	Destabilizing	0.994	D	0.503	neutral	D	0.540641798	None	None	N
K/F	0.93	likely_pathogenic	0.9172	pathogenic	-0.714	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/G	0.9517	likely_pathogenic	0.926	pathogenic	-1.294	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
K/H	0.5798	likely_pathogenic	0.5684	pathogenic	-1.673	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/I	0.6959	likely_pathogenic	0.6858	pathogenic	0.057	Stabilizing	0.997	D	0.779	deleterious	N	0.501355415	None	None	N
K/L	0.7117	likely_pathogenic	0.6543	pathogenic	0.057	Stabilizing	0.992	D	0.656	neutral	None	None	None	None	N
K/M	0.5461	ambiguous	0.4855	ambiguous	0.017	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/N	0.8802	likely_pathogenic	0.8364	pathogenic	-0.642	Destabilizing	0.998	D	0.605	neutral	D	0.522284054	None	None	N
K/P	0.9967	likely_pathogenic	0.9946	pathogenic	-0.241	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/Q	0.3943	ambiguous	0.3421	ambiguous	-0.708	Destabilizing	0.999	D	0.601	neutral	N	0.521777075	None	None	N
K/R	0.0969	likely_benign	0.0903	benign	-0.664	Destabilizing	0.994	D	0.561	neutral	N	0.465041092	None	None	N
K/S	0.9477	likely_pathogenic	0.928	pathogenic	-1.414	Destabilizing	0.983	D	0.48	neutral	None	None	None	None	N
K/T	0.883	likely_pathogenic	0.8527	pathogenic	-1.054	Destabilizing	0.543	D	0.409	neutral	N	0.513636773	None	None	N
K/V	0.7142	likely_pathogenic	0.7226	pathogenic	-0.241	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
K/W	0.909	likely_pathogenic	0.8935	pathogenic	-0.541	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/Y	0.7687	likely_pathogenic	0.7413	pathogenic	-0.219	Destabilizing	1.0	D	0.775	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.