TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20046	60361;60362;60363	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
N2AB	18405	55438;55439;55440	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
N2A	17478	52657;52658;52659	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
N2B	10981	33166;33167;33168	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
Novex-1	11106	33541;33542;33543	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
Novex-2	11173	33742;33743;33744	chr2:178591683;178591682;178591681	chr2:179456410;179456409;179456408
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-33
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.0872
• 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
Y/F	rs1290494704	-1.038	0.999	D	0.759	0.774	0.889186418864	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
Y/F	rs1290494704	-1.038	0.999	D	0.759	0.774	0.889186418864	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	2.28707E-05	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
Y/A	0.9903	likely_pathogenic	0.9878	pathogenic	-3.006	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/C	0.7932	likely_pathogenic	0.7632	pathogenic	-1.687	Destabilizing	1.0	D	0.883	deleterious	D	0.656452204	None	None	N
Y/D	0.9967	likely_pathogenic	0.9957	pathogenic	-3.753	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.67270373	None	None	N
Y/E	0.9987	likely_pathogenic	0.9983	pathogenic	-3.532	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/F	0.2083	likely_benign	0.1992	benign	-1.167	Destabilizing	0.999	D	0.759	deleterious	D	0.609596023	None	None	N
Y/G	0.9836	likely_pathogenic	0.9827	pathogenic	-3.417	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/H	0.9424	likely_pathogenic	0.9345	pathogenic	-2.364	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.67270373	None	None	N
Y/I	0.9553	likely_pathogenic	0.9291	pathogenic	-1.621	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9974	likely_pathogenic	0.9969	pathogenic	-2.365	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/L	0.8843	likely_pathogenic	0.8558	pathogenic	-1.621	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/M	0.9641	likely_pathogenic	0.9534	pathogenic	-1.392	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/N	0.9693	likely_pathogenic	0.959	pathogenic	-3.26	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.672501926	None	None	N
Y/P	0.9984	likely_pathogenic	0.9983	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
Y/Q	0.9954	likely_pathogenic	0.9941	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/R	0.9872	likely_pathogenic	0.9859	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/S	0.9715	likely_pathogenic	0.9631	pathogenic	-3.478	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.67270373	None	None	N
Y/T	0.9906	likely_pathogenic	0.9863	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/V	0.9014	likely_pathogenic	0.8635	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/W	0.668	likely_pathogenic	0.644	pathogenic	-0.524	Destabilizing	1.0	D	0.829	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.