TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30289	91090;91091;91092	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
N2AB	28648	86167;86168;86169	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
N2A	27721	83386;83387;83388	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
N2B	21224	63895;63896;63897	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
Novex-1	21349	64270;64271;64272	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
Novex-2	21416	64471;64472;64473	chr2:178552035;178552034;178552033	chr2:179416762;179416761;179416760
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: Fn3-108
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.0795
• 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/P	rs1338109334	-1.945	1.0	D	0.827	0.884	0.934516764146	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
L/P	rs1338109334	-1.945	1.0	D	0.827	0.884	0.934516764146	gnomAD-4.0.0	1.59187E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-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
L/A	0.9758	likely_pathogenic	0.9688	pathogenic	-2.781	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
L/C	0.9624	likely_pathogenic	0.9588	pathogenic	-2.478	Highly Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9996	pathogenic	-3.298	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/E	0.9987	likely_pathogenic	0.9983	pathogenic	-3.115	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/F	0.9286	likely_pathogenic	0.8838	pathogenic	-1.84	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/G	0.9967	likely_pathogenic	0.9955	pathogenic	-3.303	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/H	0.9962	likely_pathogenic	0.9943	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/I	0.4827	ambiguous	0.427	ambiguous	-1.282	Destabilizing	0.999	D	0.831	deleterious	D	0.643768896	None	None	N
L/K	0.9967	likely_pathogenic	0.9957	pathogenic	-2.22	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/M	0.5868	likely_pathogenic	0.5227	ambiguous	-1.321	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/N	0.9979	likely_pathogenic	0.9968	pathogenic	-2.539	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/P	0.9968	likely_pathogenic	0.9953	pathogenic	-1.762	Destabilizing	1.0	D	0.827	deleterious	D	0.682963643	None	None	N
L/Q	0.995	likely_pathogenic	0.993	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.682963643	None	None	N
L/R	0.9908	likely_pathogenic	0.9889	pathogenic	-1.772	Destabilizing	1.0	D	0.805	deleterious	D	0.666944282	None	None	N
L/S	0.9977	likely_pathogenic	0.9965	pathogenic	-3.238	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/T	0.974	likely_pathogenic	0.965	pathogenic	-2.909	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/V	0.5346	ambiguous	0.5047	ambiguous	-1.762	Destabilizing	0.999	D	0.837	deleterious	D	0.617645013	None	None	N
L/W	0.9952	likely_pathogenic	0.9923	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/Y	0.9946	likely_pathogenic	0.9919	pathogenic	-1.951	Destabilizing	1.0	D	0.773	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.