TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8859	26800;26801;26802	chr2:178714083;178714082;178714081	chr2:179578810;179578809;179578808
N2AB	8542	25849;25850;25851	chr2:178714083;178714082;178714081	chr2:179578810;179578809;179578808
N2A	7615	23068;23069;23070	chr2:178714083;178714082;178714081	chr2:179578810;179578809;179578808
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-74
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1656
• 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
L/I	rs1361604566	-1.245	0.884	N	0.401	0.214	0.447311733946	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
L/I	rs1361604566	-1.245	0.884	N	0.401	0.214	0.447311733946	gnomAD-4.0.0	1.59159E-06	None	None	None	None	I	None	0	0	None	0	2.77331E-05	None	0	0	0	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	0.7502	likely_pathogenic	0.8109	pathogenic	-2.168	Highly Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	I
L/C	0.8162	likely_pathogenic	0.8816	pathogenic	-1.511	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
L/D	0.9846	likely_pathogenic	0.989	pathogenic	-1.588	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
L/E	0.9358	likely_pathogenic	0.9536	pathogenic	-1.486	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
L/F	0.4859	ambiguous	0.5319	ambiguous	-1.396	Destabilizing	0.999	D	0.818	deleterious	N	0.510838832	None	None	I
L/G	0.9243	likely_pathogenic	0.9486	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
L/H	0.8691	likely_pathogenic	0.9086	pathogenic	-1.839	Destabilizing	1.0	D	0.759	deleterious	N	0.488863243	None	None	I
L/I	0.1428	likely_benign	0.1516	benign	-0.955	Destabilizing	0.884	D	0.401	neutral	N	0.48186272	None	None	I
L/K	0.8843	likely_pathogenic	0.9161	pathogenic	-1.441	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
L/M	0.2615	likely_benign	0.2938	benign	-0.854	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
L/N	0.8996	likely_pathogenic	0.9264	pathogenic	-1.401	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
L/P	0.6085	likely_pathogenic	0.6528	pathogenic	-1.332	Destabilizing	1.0	D	0.815	deleterious	N	0.379708639	None	None	I
L/Q	0.7993	likely_pathogenic	0.8621	pathogenic	-1.456	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
L/R	0.8051	likely_pathogenic	0.871	pathogenic	-0.986	Destabilizing	1.0	D	0.817	deleterious	N	0.497003544	None	None	I
L/S	0.9003	likely_pathogenic	0.9393	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
L/T	0.7637	likely_pathogenic	0.8217	pathogenic	-1.931	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
L/V	0.1874	likely_benign	0.215	benign	-1.332	Destabilizing	0.981	D	0.597	neutral	N	0.471088366	None	None	I
L/W	0.7868	likely_pathogenic	0.8408	pathogenic	-1.539	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
L/Y	0.8073	likely_pathogenic	0.8481	pathogenic	-1.302	Destabilizing	1.0	D	0.815	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.