TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6140	18643;18644;18645	chr2:178729835;178729834;178729833	chr2:179594562;179594561;179594560
N2AB	5823	17692;17693;17694	chr2:178729835;178729834;178729833	chr2:179594562;179594561;179594560
N2A	4896	14911;14912;14913	chr2:178729835;178729834;178729833	chr2:179594562;179594561;179594560
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-45
• Domain position: 36
• Structural Position: 49
• Q(SASA): 0.168
• 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
Y/C	rs1181020679	-1.379	1.0	D	0.718	0.705	0.826048732949	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
Y/C	rs1181020679	-1.379	1.0	D	0.718	0.705	0.826048732949	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85866E-06	0	0
Y/H	None	None	0.998	N	0.576	0.615	0.675278370098	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
Y/A	0.7599	likely_pathogenic	0.7499	pathogenic	-2.554	Highly Destabilizing	0.985	D	0.635	neutral	None	None	None	None	N
Y/C	0.3973	ambiguous	0.432	ambiguous	-1.072	Destabilizing	1.0	D	0.718	prob.delet.	D	0.551702065	None	None	N
Y/D	0.6495	likely_pathogenic	0.6381	pathogenic	-1.126	Destabilizing	0.998	D	0.742	deleterious	D	0.551702065	None	None	N
Y/E	0.8316	likely_pathogenic	0.8183	pathogenic	-1.038	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
Y/F	0.0737	likely_benign	0.0742	benign	-1.158	Destabilizing	0.031	N	0.211	neutral	N	0.456044342	None	None	N
Y/G	0.7017	likely_pathogenic	0.688	pathogenic	-2.871	Highly Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
Y/H	0.2386	likely_benign	0.2311	benign	-1.171	Destabilizing	0.998	D	0.576	neutral	N	0.513594224	None	None	N
Y/I	0.5446	ambiguous	0.5656	pathogenic	-1.58	Destabilizing	0.97	D	0.617	neutral	None	None	None	None	N
Y/K	0.6661	likely_pathogenic	0.6514	pathogenic	-1.13	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
Y/L	0.5002	ambiguous	0.4882	ambiguous	-1.58	Destabilizing	0.871	D	0.565	neutral	None	None	None	None	N
Y/M	0.6512	likely_pathogenic	0.644	pathogenic	-1.195	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
Y/N	0.3211	likely_benign	0.3081	benign	-1.352	Destabilizing	0.998	D	0.728	prob.delet.	N	0.512112967	None	None	N
Y/P	0.9927	likely_pathogenic	0.9937	pathogenic	-1.902	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
Y/Q	0.6508	likely_pathogenic	0.629	pathogenic	-1.363	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
Y/R	0.536	ambiguous	0.5233	ambiguous	-0.593	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
Y/S	0.408	ambiguous	0.391	ambiguous	-1.969	Destabilizing	0.998	D	0.676	prob.neutral	N	0.492007249	None	None	N
Y/T	0.6709	likely_pathogenic	0.6601	pathogenic	-1.789	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
Y/V	0.5269	ambiguous	0.5372	ambiguous	-1.902	Destabilizing	0.97	D	0.571	neutral	None	None	None	None	N
Y/W	0.5046	ambiguous	0.5216	ambiguous	-0.632	Destabilizing	0.999	D	0.577	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.