TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8607	26044;26045;26046	chr2:178715595;178715594;178715593	chr2:179580322;179580321;179580320
N2AB	8290	25093;25094;25095	chr2:178715595;178715594;178715593	chr2:179580322;179580321;179580320
N2A	7363	22312;22313;22314	chr2:178715595;178715594;178715593	chr2:179580322;179580321;179580320
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-71
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0689
• 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	rs780404365	-1.635	1.0	D	0.924	0.841	0.895674922005	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
L/R	None	None	0.999	D	0.918	0.831	0.876399648183	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85901E-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	0.7967	likely_pathogenic	0.7563	pathogenic	-2.593	Highly Destabilizing	0.95	D	0.767	deleterious	None	None	None	None	N
L/C	0.8834	likely_pathogenic	0.8653	pathogenic	-1.842	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9984	pathogenic	-3.446	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.989	likely_pathogenic	0.9859	pathogenic	-3.14	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/F	0.4164	ambiguous	0.3848	ambiguous	-1.66	Destabilizing	0.963	D	0.795	deleterious	None	None	None	None	N
L/G	0.9754	likely_pathogenic	0.9693	pathogenic	-3.15	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/H	0.9756	likely_pathogenic	0.9672	pathogenic	-2.935	Highly Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
L/I	0.1173	likely_benign	0.1011	benign	-0.904	Destabilizing	0.002	N	0.369	neutral	None	None	None	None	N
L/K	0.9831	likely_pathogenic	0.9789	pathogenic	-2.052	Highly Destabilizing	0.992	D	0.901	deleterious	None	None	None	None	N
L/M	0.174	likely_benign	0.1639	benign	-1.117	Destabilizing	0.856	D	0.774	deleterious	D	0.550020225	None	None	N
L/N	0.9918	likely_pathogenic	0.9884	pathogenic	-2.796	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/P	0.9912	likely_pathogenic	0.9889	pathogenic	-1.461	Destabilizing	1.0	D	0.924	deleterious	D	0.581001722	None	None	N
L/Q	0.95	likely_pathogenic	0.9384	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.581001722	None	None	N
L/R	0.9656	likely_pathogenic	0.9577	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.918	deleterious	D	0.581001722	None	None	N
L/S	0.9725	likely_pathogenic	0.9588	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/T	0.896	likely_pathogenic	0.8598	pathogenic	-2.782	Highly Destabilizing	0.952	D	0.83	deleterious	None	None	None	None	N
L/V	0.1972	likely_benign	0.17	benign	-1.461	Destabilizing	0.038	N	0.741	deleterious	D	0.547297973	None	None	N
L/W	0.8598	likely_pathogenic	0.8405	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/Y	0.9288	likely_pathogenic	0.9165	pathogenic	-1.853	Destabilizing	0.862	D	0.84	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.