TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8722	26389;26390;26391	chr2:178715022;178715021;178715020	chr2:179579749;179579748;179579747
N2AB	8405	25438;25439;25440	chr2:178715022;178715021;178715020	chr2:179579749;179579748;179579747
N2A	7478	22657;22658;22659	chr2:178715022;178715021;178715020	chr2:179579749;179579748;179579747
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-72
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2181
• Predicted PPI site: I

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
G/R	None	None	1.0	D	0.855	0.689	0.749798479323	gnomAD-4.0.0	1.59352E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02737E-05

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
G/A	0.6637	likely_pathogenic	0.8176	pathogenic	-0.314	Destabilizing	1.0	D	0.738	prob.delet.	D	0.592942734	None	None	I
G/C	0.9019	likely_pathogenic	0.9668	pathogenic	-0.905	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/D	0.916	likely_pathogenic	0.9597	pathogenic	-0.711	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/E	0.95	likely_pathogenic	0.9828	pathogenic	-0.887	Destabilizing	1.0	D	0.829	deleterious	D	0.54666609	None	None	I
G/F	0.9743	likely_pathogenic	0.9902	pathogenic	-1.115	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/H	0.9758	likely_pathogenic	0.9922	pathogenic	-0.503	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/I	0.965	likely_pathogenic	0.9894	pathogenic	-0.536	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/K	0.9812	likely_pathogenic	0.9939	pathogenic	-0.794	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/L	0.9637	likely_pathogenic	0.9871	pathogenic	-0.536	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/M	0.9795	likely_pathogenic	0.9932	pathogenic	-0.525	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/N	0.9523	likely_pathogenic	0.9803	pathogenic	-0.461	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/P	0.9974	likely_pathogenic	0.999	pathogenic	-0.432	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/Q	0.9579	likely_pathogenic	0.9853	pathogenic	-0.782	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/R	0.9436	likely_pathogenic	0.9801	pathogenic	-0.31	Destabilizing	1.0	D	0.855	deleterious	D	0.623325943	None	None	I
G/S	0.5768	likely_pathogenic	0.7752	pathogenic	-0.568	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/T	0.9047	likely_pathogenic	0.9617	pathogenic	-0.682	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/V	0.9341	likely_pathogenic	0.9783	pathogenic	-0.432	Destabilizing	1.0	D	0.821	deleterious	D	0.649469468	None	None	I
G/W	0.9615	likely_pathogenic	0.9852	pathogenic	-1.232	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/Y	0.9628	likely_pathogenic	0.9868	pathogenic	-0.902	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I

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.