TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24948	75067;75068;75069	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
N2AB	23307	70144;70145;70146	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
N2A	22380	67363;67364;67365	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
N2B	15883	47872;47873;47874	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
Novex-1	16008	48247;48248;48249	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
Novex-2	16075	48448;48449;48450	chr2:178571290;178571289;178571288	chr2:179436017;179436016;179436015
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: Fn3-69
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.2837
• 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/T	rs1263875134	None	0.988	D	0.741	0.476	0.397691132334	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1263875134	None	0.988	D	0.741	0.476	0.397691132334	gnomAD-4.0.0	2.56321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78785E-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	0.989	likely_pathogenic	0.9911	pathogenic	-1.514	Destabilizing	0.968	D	0.55	neutral	None	None	None	None	N
K/C	0.9726	likely_pathogenic	0.9794	pathogenic	-1.587	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
K/D	0.9987	likely_pathogenic	0.999	pathogenic	-1.832	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
K/E	0.9839	likely_pathogenic	0.9886	pathogenic	-1.559	Destabilizing	0.958	D	0.429	neutral	N	0.507337032	None	None	N
K/F	0.9977	likely_pathogenic	0.9986	pathogenic	-0.847	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
K/G	0.9882	likely_pathogenic	0.991	pathogenic	-1.961	Destabilizing	0.991	D	0.725	prob.delet.	None	None	None	None	N
K/H	0.9281	likely_pathogenic	0.944	pathogenic	-2.099	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/I	0.991	likely_pathogenic	0.994	pathogenic	-0.256	Destabilizing	0.995	D	0.852	deleterious	None	None	None	None	N
K/L	0.9698	likely_pathogenic	0.9764	pathogenic	-0.256	Destabilizing	0.991	D	0.725	prob.delet.	None	None	None	None	N
K/M	0.9322	likely_pathogenic	0.9498	pathogenic	-0.625	Destabilizing	0.999	D	0.8	deleterious	N	0.513999757	None	None	N
K/N	0.9935	likely_pathogenic	0.9958	pathogenic	-1.68	Destabilizing	0.988	D	0.646	neutral	N	0.499654484	None	None	N
K/P	0.9993	likely_pathogenic	0.9994	pathogenic	-0.655	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
K/Q	0.8371	likely_pathogenic	0.8815	pathogenic	-1.383	Destabilizing	0.988	D	0.623	neutral	N	0.478508355	None	None	N
K/R	0.1672	likely_benign	0.2024	benign	-1.111	Destabilizing	0.142	N	0.259	neutral	N	0.489369403	None	None	N
K/S	0.9939	likely_pathogenic	0.9958	pathogenic	-2.213	Highly Destabilizing	0.968	D	0.522	neutral	None	None	None	None	N
K/T	0.9865	likely_pathogenic	0.99	pathogenic	-1.7	Destabilizing	0.988	D	0.741	deleterious	D	0.524253199	None	None	N
K/V	0.9848	likely_pathogenic	0.9888	pathogenic	-0.655	Destabilizing	0.995	D	0.825	deleterious	None	None	None	None	N
K/W	0.9955	likely_pathogenic	0.9971	pathogenic	-0.927	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/Y	0.9888	likely_pathogenic	0.9931	pathogenic	-0.559	Destabilizing	0.998	D	0.857	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.