TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15973	48142;48143;48144	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
N2AB	14332	43219;43220;43221	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
N2A	13405	40438;40439;40440	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
N2B	6908	20947;20948;20949	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
Novex-1	7033	21322;21323;21324	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
Novex-2	7100	21523;21524;21525	chr2:178616972;178616971;178616970	chr2:179481699;179481698;179481697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-109
• Domain position: 6
• Structural Position: 14
• Q(SASA): 0.6977
• 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
E/K	rs375099780	0.713	0.998	N	0.557	0.338	None	gnomAD-2.1.1	2.15E-05	None	None	None	None	I	None	2.48303E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs375099780	0.713	0.998	N	0.557	0.338	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.67E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs375099780	0.713	0.998	N	0.557	0.338	None	gnomAD-4.0.0	5.58146E-06	None	None	None	None	I	None	1.20376E-04	0	None	0	0	None	0	0	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
E/A	0.5575	ambiguous	0.544	ambiguous	-0.584	Destabilizing	0.989	D	0.521	neutral	N	0.469300847	None	None	I
E/C	0.9576	likely_pathogenic	0.9617	pathogenic	-0.289	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
E/D	0.5368	ambiguous	0.5714	pathogenic	-0.619	Destabilizing	0.998	D	0.473	neutral	N	0.442736064	None	None	I
E/F	0.9745	likely_pathogenic	0.9732	pathogenic	-0.153	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
E/G	0.7879	likely_pathogenic	0.7875	pathogenic	-0.849	Destabilizing	0.999	D	0.563	neutral	N	0.51211362	None	None	I
E/H	0.865	likely_pathogenic	0.8726	pathogenic	0.028	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/I	0.75	likely_pathogenic	0.7262	pathogenic	0.108	Stabilizing	0.995	D	0.615	neutral	None	None	None	None	I
E/K	0.6378	likely_pathogenic	0.6359	pathogenic	0.078	Stabilizing	0.998	D	0.557	neutral	N	0.449729639	None	None	I
E/L	0.8382	likely_pathogenic	0.8297	pathogenic	0.108	Stabilizing	0.983	D	0.601	neutral	None	None	None	None	I
E/M	0.8276	likely_pathogenic	0.8121	pathogenic	0.219	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	I
E/N	0.747	likely_pathogenic	0.7512	pathogenic	-0.479	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/P	0.9391	likely_pathogenic	0.9441	pathogenic	-0.102	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
E/Q	0.401	ambiguous	0.3977	ambiguous	-0.394	Destabilizing	0.999	D	0.617	neutral	N	0.44127226	None	None	I
E/R	0.7495	likely_pathogenic	0.7512	pathogenic	0.404	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/S	0.631	likely_pathogenic	0.6325	pathogenic	-0.638	Destabilizing	0.996	D	0.59	neutral	None	None	None	None	I
E/T	0.5168	ambiguous	0.511	ambiguous	-0.412	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	I
E/V	0.4832	ambiguous	0.4633	ambiguous	-0.102	Destabilizing	0.733	D	0.385	neutral	N	0.446411319	None	None	I
E/W	0.9883	likely_pathogenic	0.9893	pathogenic	0.108	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/Y	0.942	likely_pathogenic	0.9434	pathogenic	0.115	Stabilizing	1.0	D	0.647	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.