TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22293	67102;67103;67104	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
N2AB	20652	62179;62180;62181	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
N2A	19725	59398;59399;59400	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
N2B	13228	39907;39908;39909	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
Novex-1	13353	40282;40283;40284	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
Novex-2	13420	40483;40484;40485	chr2:178580502;178580501;178580500	chr2:179445229;179445228;179445227
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-126
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.2127
• 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
I/T	rs766138542	-2.001	0.92	N	0.633	0.621	0.745045780685	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
I/T	rs766138542	-2.001	0.92	N	0.633	0.621	0.745045780685	gnomAD-4.0.0	1.59312E-06	None	None	None	None	I	None	0	0	None	0	2.78489E-05	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
I/A	0.8167	likely_pathogenic	0.7907	pathogenic	-2.212	Highly Destabilizing	0.079	N	0.395	neutral	None	None	None	None	I
I/C	0.8427	likely_pathogenic	0.8186	pathogenic	-1.607	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
I/D	0.9943	likely_pathogenic	0.9913	pathogenic	-1.752	Destabilizing	0.991	D	0.788	deleterious	None	None	None	None	I
I/E	0.9766	likely_pathogenic	0.968	pathogenic	-1.634	Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	I
I/F	0.5953	likely_pathogenic	0.5452	ambiguous	-1.398	Destabilizing	0.988	D	0.597	neutral	N	0.50083234	None	None	I
I/G	0.971	likely_pathogenic	0.9603	pathogenic	-2.675	Highly Destabilizing	0.884	D	0.763	deleterious	None	None	None	None	I
I/H	0.972	likely_pathogenic	0.963	pathogenic	-1.997	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
I/K	0.9378	likely_pathogenic	0.9216	pathogenic	-1.612	Destabilizing	0.982	D	0.783	deleterious	None	None	None	None	I
I/L	0.3184	likely_benign	0.2915	benign	-0.938	Destabilizing	0.509	D	0.395	neutral	N	0.497336393	None	None	I
I/M	0.214	likely_benign	0.1971	benign	-0.85	Destabilizing	0.988	D	0.569	neutral	N	0.517975544	None	None	I
I/N	0.8889	likely_pathogenic	0.8638	pathogenic	-1.608	Destabilizing	0.996	D	0.805	deleterious	D	0.536586778	None	None	I
I/P	0.9628	likely_pathogenic	0.9471	pathogenic	-1.336	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	I
I/Q	0.937	likely_pathogenic	0.922	pathogenic	-1.619	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	I
I/R	0.926	likely_pathogenic	0.901	pathogenic	-1.206	Destabilizing	0.991	D	0.804	deleterious	None	None	None	None	I
I/S	0.879	likely_pathogenic	0.8601	pathogenic	-2.365	Highly Destabilizing	0.852	D	0.726	prob.delet.	D	0.524976983	None	None	I
I/T	0.8195	likely_pathogenic	0.8102	pathogenic	-2.105	Highly Destabilizing	0.92	D	0.633	neutral	N	0.506619238	None	None	I
I/V	0.1226	likely_benign	0.1121	benign	-1.336	Destabilizing	0.061	N	0.196	neutral	N	0.427249083	None	None	I
I/W	0.9823	likely_pathogenic	0.9735	pathogenic	-1.595	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
I/Y	0.8963	likely_pathogenic	0.8779	pathogenic	-1.349	Destabilizing	0.997	D	0.685	prob.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.