TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23356	70291;70292;70293	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
N2AB	21715	65368;65369;65370	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
N2A	20788	62587;62588;62589	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
N2B	14291	43096;43097;43098	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
Novex-1	14416	43471;43472;43473	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
Novex-2	14483	43672;43673;43674	chr2:178576066;178576065;178576064	chr2:179440793;179440792;179440791
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-129
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2551
• 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
V/I	rs1207836218	-0.547	0.025	D	0.308	0.235	0.600020119452	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/I	rs1207836218	-0.547	0.025	D	0.308	0.235	0.600020119452	gnomAD-4.0.0	6.36697E-06	None	None	None	None	I	None	0	4.5731E-05	None	0	0	None	0	0	5.71857E-06	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
V/A	0.6673	likely_pathogenic	0.661	pathogenic	-1.778	Destabilizing	0.892	D	0.457	neutral	D	0.533523691	None	None	I
V/C	0.8963	likely_pathogenic	0.8706	pathogenic	-1.217	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
V/D	0.9918	likely_pathogenic	0.9899	pathogenic	-1.961	Destabilizing	0.994	D	0.676	prob.neutral	D	0.53905554	None	None	I
V/E	0.9678	likely_pathogenic	0.9577	pathogenic	-1.821	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	I
V/F	0.7913	likely_pathogenic	0.7853	pathogenic	-1.068	Destabilizing	0.967	D	0.62	neutral	N	0.508834511	None	None	I
V/G	0.8368	likely_pathogenic	0.8334	pathogenic	-2.239	Highly Destabilizing	0.983	D	0.663	neutral	D	0.538548561	None	None	I
V/H	0.9888	likely_pathogenic	0.9854	pathogenic	-1.929	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
V/I	0.143	likely_benign	0.1357	benign	-0.54	Destabilizing	0.025	N	0.308	neutral	D	0.532696972	None	None	I
V/K	0.9652	likely_pathogenic	0.9595	pathogenic	-1.607	Destabilizing	0.987	D	0.621	neutral	None	None	None	None	I
V/L	0.666	likely_pathogenic	0.6299	pathogenic	-0.54	Destabilizing	0.025	N	0.28	neutral	N	0.518383667	None	None	I
V/M	0.6579	likely_pathogenic	0.615	pathogenic	-0.455	Destabilizing	0.975	D	0.585	neutral	None	None	None	None	I
V/N	0.9691	likely_pathogenic	0.9607	pathogenic	-1.68	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	I
V/P	0.9903	likely_pathogenic	0.9889	pathogenic	-0.922	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	I
V/Q	0.9486	likely_pathogenic	0.9337	pathogenic	-1.633	Destabilizing	0.996	D	0.63	neutral	None	None	None	None	I
V/R	0.949	likely_pathogenic	0.9453	pathogenic	-1.296	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
V/S	0.8631	likely_pathogenic	0.8549	pathogenic	-2.279	Highly Destabilizing	0.987	D	0.617	neutral	None	None	None	None	I
V/T	0.6381	likely_pathogenic	0.6232	pathogenic	-2.013	Highly Destabilizing	0.916	D	0.555	neutral	None	None	None	None	I
V/W	0.9964	likely_pathogenic	0.9959	pathogenic	-1.509	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	I
V/Y	0.9769	likely_pathogenic	0.974	pathogenic	-1.135	Destabilizing	0.987	D	0.626	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.