TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29875	89848;89849;89850	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
N2AB	28234	84925;84926;84927	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
N2A	27307	82144;82145;82146	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
N2B	20810	62653;62654;62655	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
Novex-1	20935	63028;63029;63030	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
Novex-2	21002	63229;63230;63231	chr2:178553277;178553276;178553275	chr2:179418004;179418003;179418002
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-147
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.1356
• 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	None	None	0.989	D	0.463	0.436	0.327686398923	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
K/Q	rs1700097598	None	0.997	N	0.643	0.429	0.192905019026	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs1700097598	None	0.997	N	0.643	0.429	0.192905019026	gnomAD-4.0.0	6.56866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46972E-05	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	0.9455	likely_pathogenic	0.9336	pathogenic	-1.173	Destabilizing	0.996	D	0.523	neutral	None	None	None	None	N
K/C	0.9275	likely_pathogenic	0.908	pathogenic	-1.109	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
K/D	0.987	likely_pathogenic	0.9851	pathogenic	-0.817	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
K/E	0.8602	likely_pathogenic	0.8264	pathogenic	-0.572	Destabilizing	0.989	D	0.463	neutral	D	0.543439729	None	None	N
K/F	0.9533	likely_pathogenic	0.9343	pathogenic	-0.515	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/G	0.9649	likely_pathogenic	0.9581	pathogenic	-1.65	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
K/H	0.6715	likely_pathogenic	0.6353	pathogenic	-1.729	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/I	0.8239	likely_pathogenic	0.7863	pathogenic	0.144	Stabilizing	0.999	D	0.829	deleterious	N	0.515674235	None	None	N
K/L	0.8326	likely_pathogenic	0.7869	pathogenic	0.144	Stabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
K/M	0.6635	likely_pathogenic	0.5964	pathogenic	-0.068	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/N	0.9532	likely_pathogenic	0.9434	pathogenic	-1.219	Destabilizing	0.998	D	0.656	neutral	D	0.525081984	None	None	N
K/P	0.9958	likely_pathogenic	0.9951	pathogenic	-0.268	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/Q	0.5363	ambiguous	0.4771	ambiguous	-1.007	Destabilizing	0.997	D	0.643	neutral	N	0.519802065	None	None	N
K/R	0.1184	likely_benign	0.103	benign	-0.837	Destabilizing	0.217	N	0.285	neutral	N	0.485784806	None	None	N
K/S	0.9639	likely_pathogenic	0.9564	pathogenic	-1.915	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
K/T	0.8701	likely_pathogenic	0.8329	pathogenic	-1.405	Destabilizing	0.998	D	0.716	prob.delet.	D	0.524828495	None	None	N
K/V	0.8186	likely_pathogenic	0.7798	pathogenic	-0.268	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/W	0.9339	likely_pathogenic	0.9055	pathogenic	-0.422	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8865	likely_pathogenic	0.8587	pathogenic	-0.126	Destabilizing	1.0	D	0.822	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.