TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15057	45394;45395;45396	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
N2AB	13416	40471;40472;40473	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
N2A	12489	37690;37691;37692	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
N2B	5992	18199;18200;18201	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
Novex-1	6117	18574;18575;18576	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
Novex-2	6184	18775;18776;18777	chr2:178621655;178621654;178621653	chr2:179486382;179486381;179486380
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-102
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.4589
• 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
P/S	None	None	0.987	D	0.648	0.62	0.50466331119	gnomAD-4.0.0	6.84736E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99947E-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	0.0708	likely_benign	0.0698	benign	-0.502	Destabilizing	0.117	N	0.338	neutral	D	0.536685617	None	None	N
P/C	0.7053	likely_pathogenic	0.7248	pathogenic	-0.672	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
P/D	0.3698	ambiguous	0.4549	ambiguous	0.102	Stabilizing	0.998	D	0.663	neutral	None	None	None	None	N
P/E	0.2507	likely_benign	0.2839	benign	-0.005	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
P/F	0.5397	ambiguous	0.5655	pathogenic	-0.691	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/G	0.3146	likely_benign	0.3477	ambiguous	-0.637	Destabilizing	0.966	D	0.619	neutral	None	None	None	None	N
P/H	0.2524	likely_benign	0.2621	benign	-0.206	Destabilizing	1.0	D	0.671	neutral	D	0.734752435	None	None	N
P/I	0.2799	likely_benign	0.2949	benign	-0.297	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
P/K	0.3346	likely_benign	0.3601	ambiguous	-0.303	Destabilizing	0.995	D	0.688	prob.neutral	None	None	None	None	N
P/L	0.12	likely_benign	0.1268	benign	-0.297	Destabilizing	0.993	D	0.668	neutral	D	0.734752435	None	None	N
P/M	0.2972	likely_benign	0.3302	benign	-0.313	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
P/N	0.2932	likely_benign	0.3434	ambiguous	-0.07	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
P/Q	0.1635	likely_benign	0.1728	benign	-0.297	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	N
P/R	0.248	likely_benign	0.2557	benign	0.145	Stabilizing	0.997	D	0.665	neutral	D	0.746422892	None	None	N
P/S	0.1199	likely_benign	0.1247	benign	-0.52	Destabilizing	0.987	D	0.648	neutral	D	0.665143119	None	None	N
P/T	0.094	likely_benign	0.0965	benign	-0.521	Destabilizing	0.993	D	0.681	prob.neutral	D	0.675801391	None	None	N
P/V	0.1948	likely_benign	0.2098	benign	-0.33	Destabilizing	0.99	D	0.643	neutral	None	None	None	None	N
P/W	0.6982	likely_pathogenic	0.7415	pathogenic	-0.745	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
P/Y	0.4984	ambiguous	0.5352	ambiguous	-0.436	Destabilizing	1.0	D	0.707	prob.neutral	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.