TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19961	60106;60107;60108	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
N2AB	18320	55183;55184;55185	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
N2A	17393	52402;52403;52404	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
N2B	10896	32911;32912;32913	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
Novex-1	11021	33286;33287;33288	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
Novex-2	11088	33487;33488;33489	chr2:178592023;178592022;178592021	chr2:179456750;179456749;179456748
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: Fn3-32
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.2932
• 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/T	None	None	0.051	D	0.256	0.196	0.244539031024	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43386E-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
P/A	0.0841	likely_benign	0.0805	benign	-1.428	Destabilizing	0.454	N	0.496	neutral	N	0.479040553	None	None	N
P/C	0.4532	ambiguous	0.428	ambiguous	-0.762	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	N
P/D	0.2884	likely_benign	0.2562	benign	-1.303	Destabilizing	0.525	D	0.503	neutral	None	None	None	None	N
P/E	0.2198	likely_benign	0.2016	benign	-1.304	Destabilizing	0.029	N	0.159	neutral	None	None	None	None	N
P/F	0.4478	ambiguous	0.426	ambiguous	-1.079	Destabilizing	0.974	D	0.597	neutral	None	None	None	None	N
P/G	0.3161	likely_benign	0.2869	benign	-1.736	Destabilizing	0.842	D	0.573	neutral	None	None	None	None	N
P/H	0.2136	likely_benign	0.1918	benign	-1.256	Destabilizing	0.028	N	0.406	neutral	N	0.477804474	None	None	N
P/I	0.2346	likely_benign	0.2409	benign	-0.684	Destabilizing	0.949	D	0.607	neutral	None	None	None	None	N
P/K	0.2755	likely_benign	0.257	benign	-1.179	Destabilizing	0.842	D	0.484	neutral	None	None	None	None	N
P/L	0.1231	likely_benign	0.1212	benign	-0.684	Destabilizing	0.669	D	0.627	neutral	N	0.511499688	None	None	N
P/M	0.2786	likely_benign	0.2812	benign	-0.473	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
P/N	0.2459	likely_benign	0.2337	benign	-0.948	Destabilizing	0.842	D	0.609	neutral	None	None	None	None	N
P/Q	0.1566	likely_benign	0.1466	benign	-1.128	Destabilizing	0.842	D	0.579	neutral	None	None	None	None	N
P/R	0.2004	likely_benign	0.1807	benign	-0.626	Destabilizing	0.801	D	0.605	neutral	N	0.513057126	None	None	N
P/S	0.1304	likely_benign	0.123	benign	-1.424	Destabilizing	0.669	D	0.501	neutral	N	0.515828073	None	None	N
P/T	0.1158	likely_benign	0.1117	benign	-1.323	Destabilizing	0.051	N	0.256	neutral	D	0.522023326	None	None	N
P/V	0.1641	likely_benign	0.1638	benign	-0.898	Destabilizing	0.728	D	0.583	neutral	None	None	None	None	N
P/W	0.6402	likely_pathogenic	0.5928	pathogenic	-1.282	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
P/Y	0.4079	ambiguous	0.3846	ambiguous	-0.994	Destabilizing	0.949	D	0.603	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.