TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8105	24538;24539;24540	chr2:178718887;178718886;178718885	chr2:179583614;179583613;179583612
N2AB	7788	23587;23588;23589	chr2:178718887;178718886;178718885	chr2:179583614;179583613;179583612
N2A	6861	20806;20807;20808	chr2:178718887;178718886;178718885	chr2:179583614;179583613;179583612
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-66
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.265
• 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
P/R	rs1215904654	-0.024	0.984	D	0.597	0.614	0.656596202622	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/R	rs1215904654	-0.024	0.984	D	0.597	0.614	0.656596202622	gnomAD-4.0.0	3.18352E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86648E-05	0
P/S	None	None	0.251	D	0.314	0.432	0.362758974969	gnomAD-4.0.0	6.84299E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9952E-07	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
P/A	0.0775	likely_benign	0.083	benign	-0.658	Destabilizing	0.103	N	0.273	neutral	D	0.52327237	None	None	I
P/C	0.5805	likely_pathogenic	0.6067	pathogenic	-0.809	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
P/D	0.5553	ambiguous	0.5352	ambiguous	-0.474	Destabilizing	0.976	D	0.516	neutral	None	None	None	None	I
P/E	0.2878	likely_benign	0.2784	benign	-0.525	Destabilizing	0.919	D	0.497	neutral	None	None	None	None	I
P/F	0.4571	ambiguous	0.4597	ambiguous	-0.673	Destabilizing	0.988	D	0.673	neutral	None	None	None	None	I
P/G	0.3835	ambiguous	0.3861	ambiguous	-0.824	Destabilizing	0.919	D	0.517	neutral	None	None	None	None	I
P/H	0.213	likely_benign	0.213	benign	-0.137	Destabilizing	0.999	D	0.583	neutral	D	0.636620049	None	None	I
P/I	0.3201	likely_benign	0.3291	benign	-0.335	Destabilizing	0.976	D	0.665	neutral	None	None	None	None	I
P/K	0.2657	likely_benign	0.2447	benign	-0.558	Destabilizing	0.919	D	0.489	neutral	None	None	None	None	I
P/L	0.1217	likely_benign	0.123	benign	-0.335	Destabilizing	0.811	D	0.62	neutral	D	0.59924154	None	None	I
P/M	0.313	likely_benign	0.3189	benign	-0.664	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	I
P/N	0.4229	ambiguous	0.4188	ambiguous	-0.482	Destabilizing	0.976	D	0.598	neutral	None	None	None	None	I
P/Q	0.1604	likely_benign	0.1557	benign	-0.629	Destabilizing	0.988	D	0.529	neutral	None	None	None	None	I
P/R	0.1594	likely_benign	0.1561	benign	-0.085	Destabilizing	0.984	D	0.597	neutral	D	0.603945554	None	None	I
P/S	0.1237	likely_benign	0.1251	benign	-0.851	Destabilizing	0.251	N	0.314	neutral	D	0.531159182	None	None	I
P/T	0.1277	likely_benign	0.1342	benign	-0.794	Destabilizing	0.103	N	0.314	neutral	D	0.578407442	None	None	I
P/V	0.2155	likely_benign	0.2207	benign	-0.412	Destabilizing	0.851	D	0.559	neutral	None	None	None	None	I
P/W	0.6656	likely_pathogenic	0.6581	pathogenic	-0.76	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	I
P/Y	0.4254	ambiguous	0.4198	ambiguous	-0.476	Destabilizing	0.996	D	0.673	neutral	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.