TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16631	50116;50117;50118	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
N2AB	14990	45193;45194;45195	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
N2A	14063	42412;42413;42414	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
N2B	7566	22921;22922;22923	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
Novex-1	7691	23296;23297;23298	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
Novex-2	7758	23497;23498;23499	chr2:178612830;178612829;178612828	chr2:179477557;179477556;179477555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-8
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.4645
• 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
A/G	None	None	0.999	N	0.626	0.198	0.32714864917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/S	None	None	0.998	D	0.618	0.194	0.304760801415	gnomAD-4.0.0	3.18807E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86763E-05	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
A/C	0.7615	likely_pathogenic	0.744	pathogenic	-0.83	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/D	0.8904	likely_pathogenic	0.9323	pathogenic	-0.431	Destabilizing	1.0	D	0.829	deleterious	D	0.57822667	None	None	I
A/E	0.7913	likely_pathogenic	0.8515	pathogenic	-0.583	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
A/F	0.6502	likely_pathogenic	0.6615	pathogenic	-0.841	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
A/G	0.3673	ambiguous	0.3829	ambiguous	-0.231	Destabilizing	0.999	D	0.626	neutral	N	0.515632586	None	None	I
A/H	0.873	likely_pathogenic	0.887	pathogenic	-0.185	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
A/I	0.528	ambiguous	0.5739	pathogenic	-0.341	Destabilizing	0.994	D	0.709	prob.delet.	None	None	None	None	I
A/K	0.9128	likely_pathogenic	0.9416	pathogenic	-0.555	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
A/L	0.5532	ambiguous	0.5705	pathogenic	-0.341	Destabilizing	0.994	D	0.569	neutral	None	None	None	None	I
A/M	0.5475	ambiguous	0.5502	ambiguous	-0.486	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
A/N	0.7681	likely_pathogenic	0.7984	pathogenic	-0.272	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
A/P	0.9417	likely_pathogenic	0.9642	pathogenic	-0.267	Destabilizing	1.0	D	0.787	deleterious	D	0.704788778	None	None	I
A/Q	0.7856	likely_pathogenic	0.8008	pathogenic	-0.538	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/R	0.8451	likely_pathogenic	0.8911	pathogenic	-0.097	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/S	0.2434	likely_benign	0.2466	benign	-0.475	Destabilizing	0.998	D	0.618	neutral	D	0.531227498	None	None	I
A/T	0.3595	ambiguous	0.4178	ambiguous	-0.548	Destabilizing	0.996	D	0.729	prob.delet.	D	0.56730641	None	None	I
A/V	0.2285	likely_benign	0.2628	benign	-0.267	Destabilizing	0.884	D	0.446	neutral	N	0.473500229	None	None	I
A/W	0.9504	likely_pathogenic	0.963	pathogenic	-0.955	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
A/Y	0.8373	likely_pathogenic	0.8545	pathogenic	-0.623	Destabilizing	1.0	D	0.854	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.