TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32575	97948;97949;97950	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
N2AB	30934	93025;93026;93027	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
N2A	30007	90244;90245;90246	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
N2B	23510	70753;70754;70755	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
Novex-1	23635	71128;71129;71130	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
Novex-2	23702	71329;71330;71331	chr2:178541354;178541353;178541352	chr2:179406081;179406080;179406079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-125
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1152
• 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
T/P	rs746628377	-1.164	1.0	N	0.803	0.559	None	gnomAD-4.0.0	5.92665E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.80404E-04	0	0	0	3.10328E-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
T/A	0.105	likely_benign	0.1085	benign	-1.471	Destabilizing	0.999	D	0.605	neutral	N	0.45086973	None	None	N
T/C	0.2976	likely_benign	0.281	benign	-1.393	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/D	0.793	likely_pathogenic	0.787	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/E	0.5766	likely_pathogenic	0.5649	pathogenic	-1.902	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/F	0.2219	likely_benign	0.2119	benign	-1.017	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/G	0.4309	ambiguous	0.42	ambiguous	-1.834	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/H	0.3933	ambiguous	0.3807	ambiguous	-1.771	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/I	0.137	likely_benign	0.1394	benign	-0.523	Destabilizing	1.0	D	0.804	deleterious	N	0.436537783	None	None	N
T/K	0.4302	ambiguous	0.4162	ambiguous	-0.981	Destabilizing	1.0	D	0.788	deleterious	N	0.424819279	None	None	N
T/L	0.086	likely_benign	0.085	benign	-0.523	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
T/M	0.0664	likely_benign	0.0693	benign	-0.683	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/N	0.2743	likely_benign	0.269	benign	-1.571	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
T/P	0.8935	likely_pathogenic	0.8984	pathogenic	-0.811	Destabilizing	1.0	D	0.803	deleterious	N	0.489018967	None	None	N
T/Q	0.3571	ambiguous	0.3482	ambiguous	-1.444	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/R	0.316	likely_benign	0.3127	benign	-0.997	Destabilizing	1.0	D	0.809	deleterious	N	0.423568486	None	None	N
T/S	0.1524	likely_benign	0.1471	benign	-1.753	Destabilizing	0.999	D	0.595	neutral	N	0.444253189	None	None	N
T/V	0.1175	likely_benign	0.1188	benign	-0.811	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
T/W	0.5808	likely_pathogenic	0.5799	pathogenic	-1.137	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/Y	0.3001	likely_benign	0.2935	benign	-0.807	Destabilizing	1.0	D	0.811	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.