TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23121	69586;69587;69588	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
N2AB	21480	64663;64664;64665	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
N2A	20553	61882;61883;61884	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
N2B	14056	42391;42392;42393	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
Novex-1	14181	42766;42767;42768	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
Novex-2	14248	42967;42968;42969	chr2:178576974;178576973;178576972	chr2:179441701;179441700;179441699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-55
• Domain position: 82
• Structural Position: 115
• Q(SASA): 0.1988
• 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/S	None	None	1.0	D	0.856	0.637	0.53371040847	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	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
G/A	0.9308	likely_pathogenic	0.9259	pathogenic	-0.527	Destabilizing	1.0	D	0.759	deleterious	D	0.564189871	None	None	I
G/C	0.9678	likely_pathogenic	0.9671	pathogenic	-0.948	Destabilizing	1.0	D	0.879	deleterious	D	0.583561573	None	None	I
G/D	0.9776	likely_pathogenic	0.9782	pathogenic	-0.736	Destabilizing	1.0	D	0.917	deleterious	D	0.570266257	None	None	I
G/E	0.9874	likely_pathogenic	0.9887	pathogenic	-0.853	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/F	0.9961	likely_pathogenic	0.9964	pathogenic	-0.976	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
G/H	0.9903	likely_pathogenic	0.9914	pathogenic	-0.836	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/I	0.9957	likely_pathogenic	0.9964	pathogenic	-0.438	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/K	0.9894	likely_pathogenic	0.9911	pathogenic	-1.131	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/L	0.993	likely_pathogenic	0.9931	pathogenic	-0.438	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
G/M	0.9964	likely_pathogenic	0.9964	pathogenic	-0.488	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/N	0.9818	likely_pathogenic	0.9813	pathogenic	-0.81	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/P	0.9992	likely_pathogenic	0.9992	pathogenic	-0.43	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/Q	0.9756	likely_pathogenic	0.9766	pathogenic	-1.048	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/R	0.9629	likely_pathogenic	0.969	pathogenic	-0.688	Destabilizing	1.0	D	0.917	deleterious	D	0.571026726	None	None	I
G/S	0.8232	likely_pathogenic	0.8233	pathogenic	-1.013	Destabilizing	1.0	D	0.856	deleterious	D	0.570266257	None	None	I
G/T	0.9797	likely_pathogenic	0.9795	pathogenic	-1.055	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/V	0.992	likely_pathogenic	0.9929	pathogenic	-0.43	Destabilizing	1.0	D	0.895	deleterious	D	0.550707198	None	None	I
G/W	0.9918	likely_pathogenic	0.9931	pathogenic	-1.202	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/Y	0.9936	likely_pathogenic	0.994	pathogenic	-0.843	Destabilizing	1.0	D	0.9	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.