TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23075	69448;69449;69450	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
N2AB	21434	64525;64526;64527	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
N2A	20507	61744;61745;61746	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
N2B	14010	42253;42254;42255	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
Novex-1	14135	42628;42629;42630	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
Novex-2	14202	42829;42830;42831	chr2:178577112;178577111;178577110	chr2:179441839;179441838;179441837
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: Fn3-55
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1402
• 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/S	None	None	1.0	D	0.891	0.897	0.92303318158	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9975	likely_pathogenic	0.9977	pathogenic	-3.339	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/C	0.9008	likely_pathogenic	0.9161	pathogenic	-1.894	Destabilizing	1.0	D	0.854	deleterious	D	0.678586464	None	None	N
Y/D	0.9986	likely_pathogenic	0.9988	pathogenic	-3.594	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.678788269	None	None	N
Y/E	0.9996	likely_pathogenic	0.9996	pathogenic	-3.366	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/F	0.1586	likely_benign	0.1847	benign	-1.255	Destabilizing	0.999	D	0.677	prob.neutral	D	0.584379413	None	None	N
Y/G	0.9948	likely_pathogenic	0.9948	pathogenic	-3.769	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/H	0.9739	likely_pathogenic	0.9784	pathogenic	-2.469	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.662163495	None	None	N
Y/I	0.9777	likely_pathogenic	0.9812	pathogenic	-1.888	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9993	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.95	likely_pathogenic	0.9545	pathogenic	-1.888	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
Y/M	0.984	likely_pathogenic	0.9856	pathogenic	-1.682	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/N	0.9896	likely_pathogenic	0.9896	pathogenic	-3.07	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.678586464	None	None	N
Y/P	0.9995	likely_pathogenic	0.9995	pathogenic	-2.391	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/Q	0.9987	likely_pathogenic	0.9989	pathogenic	-2.783	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/R	0.9958	likely_pathogenic	0.996	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9917	likely_pathogenic	0.9922	pathogenic	-3.427	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.678586464	None	None	N
Y/T	0.9971	likely_pathogenic	0.9971	pathogenic	-3.071	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.9547	likely_pathogenic	0.958	pathogenic	-2.391	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.7406	likely_pathogenic	0.7892	pathogenic	-0.454	Destabilizing	1.0	D	0.795	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.