TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32916	98971;98972;98973	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
N2AB	31275	94048;94049;94050	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
N2A	30348	91267;91268;91269	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
N2B	23851	71776;71777;71778	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
Novex-1	23976	72151;72152;72153	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
Novex-2	24043	72352;72353;72354	chr2:178539189;178539188;178539187	chr2:179403916;179403915;179403914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-128
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.1705
• 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/F	None	None	1.0	N	0.711	0.479	0.571278246138	gnomAD-4.0.0	2.05265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69846E-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	0.9748	likely_pathogenic	0.976	pathogenic	-2.428	Highly Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
L/C	0.9607	likely_pathogenic	0.9521	pathogenic	-1.345	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-2.951	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/E	0.9991	likely_pathogenic	0.9991	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/F	0.8479	likely_pathogenic	0.8047	pathogenic	-1.416	Destabilizing	1.0	D	0.711	prob.delet.	N	0.513481049	None	None	N
L/G	0.9979	likely_pathogenic	0.9979	pathogenic	-3.054	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/H	0.998	likely_pathogenic	0.9978	pathogenic	-2.908	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/I	0.173	likely_benign	0.1514	benign	-0.541	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
L/K	0.9986	likely_pathogenic	0.9985	pathogenic	-1.627	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/M	0.508	ambiguous	0.4566	ambiguous	-0.687	Destabilizing	1.0	D	0.677	prob.neutral	D	0.524192244	None	None	N
L/N	0.999	likely_pathogenic	0.999	pathogenic	-2.385	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/P	0.9991	likely_pathogenic	0.9992	pathogenic	-1.161	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/Q	0.9966	likely_pathogenic	0.9967	pathogenic	-1.949	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/R	0.9966	likely_pathogenic	0.9968	pathogenic	-1.917	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/S	0.9979	likely_pathogenic	0.9981	pathogenic	-2.898	Highly Destabilizing	1.0	D	0.794	deleterious	D	0.556882035	None	None	N
L/T	0.9851	likely_pathogenic	0.9859	pathogenic	-2.381	Highly Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/V	0.2129	likely_benign	0.2082	benign	-1.161	Destabilizing	0.999	D	0.602	neutral	N	0.474312208	None	None	N
L/W	0.9951	likely_pathogenic	0.9937	pathogenic	-1.792	Destabilizing	1.0	D	0.756	deleterious	D	0.556882035	None	None	N
L/Y	0.9938	likely_pathogenic	0.9916	pathogenic	-1.56	Destabilizing	1.0	D	0.707	prob.neutral	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.