TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27323	82192;82193;82194	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
N2AB	25682	77269;77270;77271	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
N2A	24755	74488;74489;74490	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
N2B	18258	54997;54998;54999	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
Novex-1	18383	55372;55373;55374	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
Novex-2	18450	55573;55574;55575	chr2:178564165;178564164;178564163	chr2:179428892;179428891;179428890
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-140
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1229
• 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
M/T	rs1176526187	-1.718	0.994	N	0.691	0.485	0.724833077695	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
M/T	rs1176526187	-1.718	0.994	N	0.691	0.485	0.724833077695	gnomAD-4.0.0	3.18262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86541E-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
M/A	0.3817	ambiguous	0.4427	ambiguous	-2.325	Highly Destabilizing	0.989	D	0.675	neutral	None	None	None	None	N
M/C	0.617	likely_pathogenic	0.6536	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
M/D	0.8969	likely_pathogenic	0.9378	pathogenic	-1.328	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
M/E	0.5608	ambiguous	0.6437	pathogenic	-1.217	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
M/F	0.2774	likely_benign	0.3248	benign	-0.976	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
M/G	0.6307	likely_pathogenic	0.7166	pathogenic	-2.734	Highly Destabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
M/H	0.5575	ambiguous	0.6389	pathogenic	-1.923	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
M/I	0.2343	likely_benign	0.2825	benign	-1.201	Destabilizing	0.985	D	0.639	neutral	N	0.407399459	None	None	N
M/K	0.2168	likely_benign	0.2538	benign	-1.247	Destabilizing	0.994	D	0.687	prob.neutral	D	0.522957194	None	None	N
M/L	0.1088	likely_benign	0.1203	benign	-1.201	Destabilizing	0.927	D	0.394	neutral	N	0.434874062	None	None	N
M/N	0.5998	likely_pathogenic	0.696	pathogenic	-1.248	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
M/P	0.9435	likely_pathogenic	0.965	pathogenic	-1.552	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
M/Q	0.3194	likely_benign	0.3677	ambiguous	-1.19	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
M/R	0.2207	likely_benign	0.266	benign	-0.923	Destabilizing	0.998	D	0.726	prob.delet.	D	0.522783835	None	None	N
M/S	0.4639	ambiguous	0.5341	ambiguous	-1.912	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
M/T	0.1815	likely_benign	0.2139	benign	-1.678	Destabilizing	0.994	D	0.691	prob.neutral	N	0.447285999	None	None	N
M/V	0.086	likely_benign	0.0939	benign	-1.552	Destabilizing	0.985	D	0.562	neutral	N	0.44576306	None	None	N
M/W	0.541	ambiguous	0.6005	pathogenic	-1.009	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
M/Y	0.5026	ambiguous	0.5805	pathogenic	-1.078	Destabilizing	0.999	D	0.746	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.