TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24789	74590;74591;74592	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
N2AB	23148	69667;69668;69669	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
N2A	22221	66886;66887;66888	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
N2B	15724	47395;47396;47397	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
Novex-1	15849	47770;47771;47772	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
Novex-2	15916	47971;47972;47973	chr2:178571767;178571766;178571765	chr2:179436494;179436493;179436492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-133
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3047
• 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
K/E	rs374382352	-0.884	0.892	N	0.573	0.396	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	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	0.3105	likely_benign	0.3127	benign	-0.907	Destabilizing	0.845	D	0.618	neutral	None	None	None	None	N
K/C	0.5041	ambiguous	0.5205	ambiguous	-1.099	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
K/D	0.6345	likely_pathogenic	0.644	pathogenic	-1.237	Destabilizing	0.975	D	0.701	prob.neutral	None	None	None	None	N
K/E	0.1774	likely_benign	0.1744	benign	-1.03	Destabilizing	0.892	D	0.573	neutral	N	0.472376445	None	None	N
K/F	0.6794	likely_pathogenic	0.6891	pathogenic	-0.273	Destabilizing	0.987	D	0.788	deleterious	None	None	None	None	N
K/G	0.4993	ambiguous	0.5009	ambiguous	-1.355	Destabilizing	0.916	D	0.712	prob.delet.	None	None	None	None	N
K/H	0.1949	likely_benign	0.197	benign	-1.715	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
K/I	0.2629	likely_benign	0.2628	benign	0.313	Stabilizing	0.967	D	0.767	deleterious	N	0.433551485	None	None	N
K/L	0.2846	likely_benign	0.2826	benign	0.313	Stabilizing	0.845	D	0.675	prob.neutral	None	None	None	None	N
K/M	0.1738	likely_benign	0.1749	benign	0.06	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.3342	likely_benign	0.3446	ambiguous	-1.392	Destabilizing	0.967	D	0.627	neutral	N	0.513108346	None	None	N
K/P	0.9442	likely_pathogenic	0.946	pathogenic	-0.066	Destabilizing	0.987	D	0.749	deleterious	None	None	None	None	N
K/Q	0.1097	likely_benign	0.1079	benign	-1.221	Destabilizing	0.983	D	0.661	neutral	N	0.517300658	None	None	N
K/R	0.0842	likely_benign	0.0834	benign	-1.182	Destabilizing	0.892	D	0.547	neutral	N	0.479110416	None	None	N
K/S	0.288	likely_benign	0.2957	benign	-1.897	Destabilizing	0.845	D	0.589	neutral	None	None	None	None	N
K/T	0.0975	likely_benign	0.0973	benign	-1.462	Destabilizing	0.025	N	0.401	neutral	N	0.388893843	None	None	N
K/V	0.2511	likely_benign	0.2473	benign	-0.066	Destabilizing	0.845	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.7168	likely_pathogenic	0.7373	pathogenic	-0.331	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.5333	ambiguous	0.5415	ambiguous	0.024	Stabilizing	0.996	D	0.773	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.