TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6597	20014;20015;20016	chr2:178727789;178727788;178727787	chr2:179592516;179592515;179592514
N2AB	6280	19063;19064;19065	chr2:178727789;178727788;178727787	chr2:179592516;179592515;179592514
N2A	5353	16282;16283;16284	chr2:178727789;178727788;178727787	chr2:179592516;179592515;179592514
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: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-50
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1195
• 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
L/I	None	None	0.64	N	0.714	0.141	0.39843156188	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
L/P	rs745676008	-1.095	0.995	N	0.83	0.572	0.690133245405	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
L/P	rs745676008	-1.095	0.995	N	0.83	0.572	0.690133245405	gnomAD-4.0.0	2.6012E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.41923E-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
L/A	0.6269	likely_pathogenic	0.5724	pathogenic	-2.31	Highly Destabilizing	0.851	D	0.737	prob.delet.	None	None	None	None	N
L/C	0.6778	likely_pathogenic	0.6344	pathogenic	-1.712	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/D	0.9912	likely_pathogenic	0.9881	pathogenic	-1.775	Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
L/E	0.94	likely_pathogenic	0.9217	pathogenic	-1.517	Destabilizing	0.988	D	0.835	deleterious	None	None	None	None	N
L/F	0.2033	likely_benign	0.1987	benign	-1.302	Destabilizing	0.034	N	0.313	neutral	None	None	None	None	N
L/G	0.8987	likely_pathogenic	0.8732	pathogenic	-2.882	Highly Destabilizing	0.988	D	0.813	deleterious	None	None	None	None	N
L/H	0.7799	likely_pathogenic	0.7437	pathogenic	-2.299	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
L/I	0.1075	likely_benign	0.114	benign	-0.648	Destabilizing	0.64	D	0.714	prob.delet.	N	0.365358049	None	None	N
L/K	0.9137	likely_pathogenic	0.9015	pathogenic	-1.456	Destabilizing	0.988	D	0.828	deleterious	None	None	None	None	N
L/M	0.1803	likely_benign	0.1758	benign	-0.774	Destabilizing	0.988	D	0.762	deleterious	None	None	None	None	N
L/N	0.944	likely_pathogenic	0.9248	pathogenic	-1.792	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
L/P	0.8883	likely_pathogenic	0.8794	pathogenic	-1.184	Destabilizing	0.995	D	0.83	deleterious	N	0.457465707	None	None	N
L/Q	0.7201	likely_pathogenic	0.6878	pathogenic	-1.552	Destabilizing	0.995	D	0.803	deleterious	N	0.482246722	None	None	N
L/R	0.8135	likely_pathogenic	0.7855	pathogenic	-1.432	Destabilizing	0.995	D	0.817	deleterious	N	0.482246722	None	None	N
L/S	0.8253	likely_pathogenic	0.7692	pathogenic	-2.652	Highly Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	N
L/T	0.6516	likely_pathogenic	0.5963	pathogenic	-2.227	Highly Destabilizing	0.919	D	0.809	deleterious	None	None	None	None	N
L/V	0.098	likely_benign	0.1042	benign	-1.184	Destabilizing	0.026	N	0.319	neutral	N	0.333373343	None	None	N
L/W	0.5897	likely_pathogenic	0.572	pathogenic	-1.545	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/Y	0.707	likely_pathogenic	0.6708	pathogenic	-1.279	Destabilizing	0.952	D	0.829	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.