TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8106	24541;24542;24543	chr2:178718884;178718883;178718882	chr2:179583611;179583610;179583609
N2AB	7789	23590;23591;23592	chr2:178718884;178718883;178718882	chr2:179583611;179583610;179583609
N2A	6862	20809;20810;20811	chr2:178718884;178718883;178718882	chr2:179583611;179583610;179583609
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: 29
• Structural Position: 43
• Q(SASA): 0.7387
• 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/L	None	None	1.0	N	0.689	0.472	0.688445511621	gnomAD-4.0.0	6.84299E-07	None	None	None	None	I	None	0	0	None	0	2.52232E-05	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
P/A	0.2035	likely_benign	0.2158	benign	-0.684	Destabilizing	1.0	D	0.661	neutral	N	0.497200446	None	None	I
P/C	0.7976	likely_pathogenic	0.8096	pathogenic	-0.571	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/D	0.6398	likely_pathogenic	0.6485	pathogenic	-0.626	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/E	0.5146	ambiguous	0.5301	ambiguous	-0.707	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	I
P/F	0.7772	likely_pathogenic	0.7789	pathogenic	-0.761	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
P/G	0.5794	likely_pathogenic	0.5807	pathogenic	-0.858	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
P/H	0.4245	ambiguous	0.4492	ambiguous	-0.39	Destabilizing	1.0	D	0.639	neutral	D	0.528435433	None	None	I
P/I	0.6011	likely_pathogenic	0.6172	pathogenic	-0.351	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/K	0.5768	likely_pathogenic	0.6035	pathogenic	-0.64	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/L	0.3061	likely_benign	0.3057	benign	-0.351	Destabilizing	1.0	D	0.689	prob.neutral	N	0.507101947	None	None	I
P/M	0.6203	likely_pathogenic	0.6329	pathogenic	-0.459	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
P/N	0.5548	ambiguous	0.5655	pathogenic	-0.337	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
P/Q	0.386	ambiguous	0.4025	ambiguous	-0.56	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
P/R	0.3735	ambiguous	0.3943	ambiguous	-0.116	Destabilizing	1.0	D	0.671	neutral	N	0.507101947	None	None	I
P/S	0.2912	likely_benign	0.3	benign	-0.674	Destabilizing	1.0	D	0.677	prob.neutral	N	0.511772755	None	None	I
P/T	0.2592	likely_benign	0.2734	benign	-0.655	Destabilizing	1.0	D	0.673	neutral	N	0.497098314	None	None	I
P/V	0.4363	ambiguous	0.4517	ambiguous	-0.428	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/W	0.8898	likely_pathogenic	0.8871	pathogenic	-0.864	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
P/Y	0.7096	likely_pathogenic	0.7269	pathogenic	-0.577	Destabilizing	1.0	D	0.639	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.