TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33092	99499;99500;99501	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
N2AB	31451	94576;94577;94578	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
N2A	30524	91795;91796;91797	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
N2B	24027	72304;72305;72306	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
Novex-1	24152	72679;72680;72681	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
Novex-2	24219	72880;72881;72882	chr2:178538555;178538554;178538553	chr2:179403282;179403281;179403280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-129
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.7933
• 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
K/N	rs778385575	0.236	0.693	N	0.715	0.26	0.311079019809	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
K/N	rs778385575	0.236	0.693	N	0.715	0.26	0.311079019809	gnomAD-4.0.0	1.59867E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44388E-05	0
K/Q	None	None	0.531	D	0.737	0.213	0.27855597813	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.7393	likely_pathogenic	0.7691	pathogenic	-0.409	Destabilizing	0.46	N	0.654	prob.neutral	None	None	None	None	I
K/C	0.8741	likely_pathogenic	0.8967	pathogenic	-0.457	Destabilizing	0.986	D	0.775	deleterious	None	None	None	None	I
K/D	0.935	likely_pathogenic	0.944	pathogenic	0.114	Stabilizing	0.749	D	0.753	deleterious	None	None	None	None	I
K/E	0.5884	likely_pathogenic	0.6131	pathogenic	0.177	Stabilizing	0.244	N	0.658	prob.neutral	N	0.514700283	None	None	I
K/F	0.9406	likely_pathogenic	0.9532	pathogenic	-0.367	Destabilizing	0.958	D	0.736	deleterious	None	None	None	None	I
K/G	0.8458	likely_pathogenic	0.8724	pathogenic	-0.71	Destabilizing	0.749	D	0.562	neutral	None	None	None	None	I
K/H	0.5573	ambiguous	0.6257	pathogenic	-1.085	Destabilizing	0.958	D	0.743	deleterious	None	None	None	None	I
K/I	0.6741	likely_pathogenic	0.6948	pathogenic	0.338	Stabilizing	0.858	D	0.759	deleterious	None	None	None	None	I
K/L	0.6792	likely_pathogenic	0.7106	pathogenic	0.338	Stabilizing	0.749	D	0.562	neutral	None	None	None	None	I
K/M	0.5445	ambiguous	0.5788	pathogenic	0.288	Stabilizing	0.981	D	0.755	deleterious	N	0.505910228	None	None	I
K/N	0.8023	likely_pathogenic	0.8338	pathogenic	-0.145	Destabilizing	0.693	D	0.715	prob.delet.	N	0.492085111	None	None	I
K/P	0.9033	likely_pathogenic	0.9127	pathogenic	0.12	Stabilizing	0.858	D	0.765	deleterious	None	None	None	None	I
K/Q	0.2697	likely_benign	0.3013	benign	-0.312	Destabilizing	0.531	D	0.737	deleterious	D	0.534326194	None	None	I
K/R	0.106	likely_benign	0.1216	benign	-0.346	Destabilizing	0.005	N	0.437	neutral	N	0.499789546	None	None	I
K/S	0.7797	likely_pathogenic	0.8144	pathogenic	-0.815	Destabilizing	0.46	N	0.712	prob.delet.	None	None	None	None	I
K/T	0.4227	ambiguous	0.4452	ambiguous	-0.563	Destabilizing	0.693	D	0.672	prob.neutral	N	0.493922366	None	None	I
K/V	0.6301	likely_pathogenic	0.6521	pathogenic	0.12	Stabilizing	0.749	D	0.711	prob.delet.	None	None	None	None	I
K/W	0.9399	likely_pathogenic	0.9583	pathogenic	-0.241	Destabilizing	0.986	D	0.783	deleterious	None	None	None	None	I
K/Y	0.8908	likely_pathogenic	0.9163	pathogenic	0.077	Stabilizing	0.858	D	0.757	deleterious	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.