TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6927	21004;21005;21006	chr2:178725425;178725424;178725423	chr2:179590152;179590151;179590150
N2AB	6610	20053;20054;20055	chr2:178725425;178725424;178725423	chr2:179590152;179590151;179590150
N2A	5683	17272;17273;17274	chr2:178725425;178725424;178725423	chr2:179590152;179590151;179590150
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-53
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0652
• 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/R	rs767021612	-1.112	1.0	D	0.907	0.795	0.865491910662	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	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	0.9156	likely_pathogenic	0.9193	pathogenic	-1.248	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
C/D	0.9997	likely_pathogenic	0.9998	pathogenic	-1.638	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
C/E	0.9997	likely_pathogenic	0.9998	pathogenic	-1.378	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/F	0.7965	likely_pathogenic	0.7877	pathogenic	-0.648	Destabilizing	1.0	D	0.89	deleterious	D	0.542773344	None	None	N
C/G	0.8496	likely_pathogenic	0.8579	pathogenic	-1.591	Destabilizing	1.0	D	0.877	deleterious	D	0.544294281	None	None	N
C/H	0.9976	likely_pathogenic	0.9981	pathogenic	-1.774	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
C/I	0.8084	likely_pathogenic	0.8301	pathogenic	-0.306	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
C/K	0.9997	likely_pathogenic	0.9998	pathogenic	-0.868	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
C/L	0.6937	likely_pathogenic	0.6937	pathogenic	-0.306	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
C/M	0.9392	likely_pathogenic	0.9448	pathogenic	-0.16	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
C/N	0.9973	likely_pathogenic	0.9979	pathogenic	-1.62	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
C/P	0.9988	likely_pathogenic	0.999	pathogenic	-0.601	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
C/Q	0.9983	likely_pathogenic	0.9987	pathogenic	-1.067	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
C/R	0.9954	likely_pathogenic	0.9964	pathogenic	-1.43	Destabilizing	1.0	D	0.907	deleterious	D	0.544294281	None	None	N
C/S	0.9628	likely_pathogenic	0.9678	pathogenic	-1.822	Destabilizing	1.0	D	0.808	deleterious	D	0.544294281	None	None	N
C/T	0.9704	likely_pathogenic	0.9741	pathogenic	-1.394	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
C/V	0.7326	likely_pathogenic	0.7422	pathogenic	-0.601	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
C/W	0.9879	likely_pathogenic	0.9903	pathogenic	-1.154	Destabilizing	1.0	D	0.877	deleterious	D	0.544294281	None	None	N
C/Y	0.9657	likely_pathogenic	0.968	pathogenic	-0.882	Destabilizing	1.0	D	0.904	deleterious	D	0.544294281	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.