TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6401	19426;19427;19428	chr2:178728725;178728724;178728723	chr2:179593452;179593451;179593450
N2AB	6084	18475;18476;18477	chr2:178728725;178728724;178728723	chr2:179593452;179593451;179593450
N2A	5157	15694;15695;15696	chr2:178728725;178728724;178728723	chr2:179593452;179593451;179593450
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: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-48
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4929
• 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/L	rs779496338	-0.256	0.998	N	0.733	0.327	0.499665682712	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
P/L	rs779496338	-0.256	0.998	N	0.733	0.327	0.499665682712	gnomAD-4.0.0	1.59847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4348E-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	0.1095	likely_benign	0.1357	benign	-1.263	Destabilizing	0.996	D	0.579	neutral	N	0.48941697	None	None	N
P/C	0.7266	likely_pathogenic	0.7593	pathogenic	-0.892	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/D	0.6432	likely_pathogenic	0.711	pathogenic	-1.099	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/E	0.4674	ambiguous	0.521	ambiguous	-1.147	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/F	0.5724	likely_pathogenic	0.6548	pathogenic	-1.126	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/G	0.4896	ambiguous	0.5833	pathogenic	-1.524	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/H	0.3388	likely_benign	0.3956	ambiguous	-0.987	Destabilizing	1.0	D	0.813	deleterious	N	0.472088076	None	None	N
P/I	0.4104	ambiguous	0.4454	ambiguous	-0.671	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
P/K	0.5342	ambiguous	0.5874	pathogenic	-0.956	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/L	0.1793	likely_benign	0.213	benign	-0.671	Destabilizing	0.998	D	0.733	prob.delet.	N	0.467795661	None	None	N
P/M	0.3995	ambiguous	0.4525	ambiguous	-0.475	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/N	0.4819	ambiguous	0.561	ambiguous	-0.71	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/Q	0.2854	likely_benign	0.3379	benign	-0.967	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/R	0.3393	likely_benign	0.3912	ambiguous	-0.364	Destabilizing	1.0	D	0.855	deleterious	N	0.509714885	None	None	N
P/S	0.1651	likely_benign	0.2165	benign	-1.203	Destabilizing	0.999	D	0.805	deleterious	N	0.450183792	None	None	N
P/T	0.135	likely_benign	0.1672	benign	-1.148	Destabilizing	0.999	D	0.75	deleterious	N	0.44793292	None	None	N
P/V	0.2846	likely_benign	0.326	benign	-0.833	Destabilizing	0.91	D	0.391	neutral	None	None	None	None	N
P/W	0.7792	likely_pathogenic	0.8406	pathogenic	-1.235	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/Y	0.5993	likely_pathogenic	0.6695	pathogenic	-0.952	Destabilizing	1.0	D	0.847	deleterious	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.