TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35675	107248;107249;107250	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
N2AB	34034	102325;102326;102327	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
N2A	33107	99544;99545;99546	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
N2B	26610	80053;80054;80055	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
Novex-1	26735	80428;80429;80430	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
Novex-2	26802	80629;80630;80631	chr2:178528728;178528727;178528726	chr2:179393455;179393454;179393453
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-167
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.13
• 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	None	None	0.999	N	0.876	0.543	0.69911688974	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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	0.9109	likely_pathogenic	0.9205	pathogenic	-2.383	Highly Destabilizing	0.985	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.9388	likely_pathogenic	0.9527	pathogenic	-1.476	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.999	pathogenic	-3.049	Highly Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
L/E	0.9931	likely_pathogenic	0.993	pathogenic	-2.712	Highly Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
L/F	0.3694	ambiguous	0.3947	ambiguous	-1.45	Destabilizing	0.997	D	0.701	prob.neutral	N	0.455128252	None	None	N
L/G	0.9874	likely_pathogenic	0.9885	pathogenic	-3.01	Highly Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
L/H	0.9646	likely_pathogenic	0.9675	pathogenic	-2.892	Highly Destabilizing	1.0	D	0.858	deleterious	N	0.456861835	None	None	N
L/I	0.179	likely_benign	0.1795	benign	-0.501	Destabilizing	0.4	N	0.44	neutral	N	0.437929357	None	None	N
L/K	0.9852	likely_pathogenic	0.9844	pathogenic	-1.685	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
L/M	0.3719	ambiguous	0.3842	ambiguous	-0.665	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
L/N	0.9939	likely_pathogenic	0.9942	pathogenic	-2.444	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/P	0.9914	likely_pathogenic	0.9914	pathogenic	-1.119	Destabilizing	0.999	D	0.876	deleterious	N	0.457208551	None	None	N
L/Q	0.971	likely_pathogenic	0.9711	pathogenic	-2.029	Highly Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
L/R	0.967	likely_pathogenic	0.9661	pathogenic	-1.927	Destabilizing	0.997	D	0.855	deleterious	N	0.457035193	None	None	N
L/S	0.9822	likely_pathogenic	0.9851	pathogenic	-2.976	Highly Destabilizing	0.971	D	0.807	deleterious	None	None	None	None	N
L/T	0.9522	likely_pathogenic	0.9599	pathogenic	-2.462	Highly Destabilizing	0.469	N	0.624	neutral	None	None	None	None	N
L/V	0.2372	likely_benign	0.2464	benign	-1.119	Destabilizing	0.911	D	0.629	neutral	N	0.456515118	None	None	N
L/W	0.8688	likely_pathogenic	0.8818	pathogenic	-1.879	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/Y	0.8619	likely_pathogenic	0.8861	pathogenic	-1.604	Destabilizing	0.999	D	0.764	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.