TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9091	27496;27497;27498	chr2:178712754;178712753;178712752	chr2:179577481;179577480;179577479
N2AB	8774	26545;26546;26547	chr2:178712754;178712753;178712752	chr2:179577481;179577480;179577479
N2A	7847	23764;23765;23766	chr2:178712754;178712753;178712752	chr2:179577481;179577480;179577479
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-76
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0698
• 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
C/W	rs375546576	-1.542	1.0	D	0.884	0.566	0.797395815551	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66389E-04
C/W	rs375546576	-1.542	1.0	D	0.884	0.566	0.797395815551	gnomAD-4.0.0	6.84212E-07	None	None	None	None	N	None	2.98793E-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
C/A	0.8075	likely_pathogenic	0.8856	pathogenic	-1.396	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
C/D	0.9985	likely_pathogenic	0.9995	pathogenic	-1.067	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/E	0.999	likely_pathogenic	0.9997	pathogenic	-0.821	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
C/F	0.7121	likely_pathogenic	0.8482	pathogenic	-0.855	Destabilizing	1.0	D	0.901	deleterious	D	0.566802628	None	None	N
C/G	0.6848	likely_pathogenic	0.8281	pathogenic	-1.76	Destabilizing	1.0	D	0.893	deleterious	D	0.568323565	None	None	N
C/H	0.9932	likely_pathogenic	0.9977	pathogenic	-1.988	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
C/I	0.8058	likely_pathogenic	0.8793	pathogenic	-0.41	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
C/K	0.9992	likely_pathogenic	0.9997	pathogenic	-0.526	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
C/L	0.6943	likely_pathogenic	0.7899	pathogenic	-0.41	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
C/M	0.8934	likely_pathogenic	0.9371	pathogenic	0.174	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
C/N	0.9901	likely_pathogenic	0.9961	pathogenic	-1.173	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
C/P	0.998	likely_pathogenic	0.9992	pathogenic	-0.716	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
C/Q	0.996	likely_pathogenic	0.9986	pathogenic	-0.669	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
C/R	0.9887	likely_pathogenic	0.996	pathogenic	-1.102	Destabilizing	1.0	D	0.917	deleterious	D	0.568323565	None	None	N
C/S	0.8833	likely_pathogenic	0.947	pathogenic	-1.454	Destabilizing	1.0	D	0.819	deleterious	D	0.568323565	None	None	N
C/T	0.9353	likely_pathogenic	0.9649	pathogenic	-1.012	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
C/V	0.6778	likely_pathogenic	0.7475	pathogenic	-0.716	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
C/W	0.9741	likely_pathogenic	0.9912	pathogenic	-1.228	Destabilizing	1.0	D	0.884	deleterious	D	0.568323565	None	None	N
C/Y	0.9318	likely_pathogenic	0.9754	pathogenic	-0.983	Destabilizing	1.0	D	0.913	deleterious	D	0.568323565	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.