TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26820	80683;80684;80685	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
N2AB	25179	75760;75761;75762	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
N2A	24252	72979;72980;72981	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
N2B	17755	53488;53489;53490	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
Novex-1	17880	53863;53864;53865	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
Novex-2	17947	54064;54065;54066	chr2:178565674;178565673;178565672	chr2:179430401;179430400;179430399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-83
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1062
• 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
Q/K	None	None	0.982	N	0.502	0.3	0.227260227426	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
Q/A	0.3818	ambiguous	0.3558	ambiguous	-1.139	Destabilizing	0.989	D	0.567	neutral	None	None	None	None	N
Q/C	0.6388	likely_pathogenic	0.616	pathogenic	-0.627	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
Q/D	0.924	likely_pathogenic	0.9087	pathogenic	-1.979	Destabilizing	0.994	D	0.505	neutral	None	None	None	None	N
Q/E	0.2033	likely_benign	0.1839	benign	-1.718	Destabilizing	0.987	D	0.531	neutral	N	0.501183907	None	None	N
Q/F	0.8074	likely_pathogenic	0.8023	pathogenic	-0.656	Destabilizing	0.994	D	0.781	deleterious	None	None	None	None	N
Q/G	0.6023	likely_pathogenic	0.5663	pathogenic	-1.554	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
Q/H	0.5243	ambiguous	0.5109	ambiguous	-1.322	Destabilizing	0.998	D	0.543	neutral	N	0.47867662	None	None	N
Q/I	0.4981	ambiguous	0.4602	ambiguous	-0.009	Destabilizing	0.985	D	0.678	prob.neutral	None	None	None	None	N
Q/K	0.1679	likely_benign	0.1482	benign	-0.547	Destabilizing	0.982	D	0.502	neutral	N	0.444386475	None	None	N
Q/L	0.1302	likely_benign	0.1255	benign	-0.009	Destabilizing	0.079	N	0.388	neutral	N	0.470266354	None	None	N
Q/M	0.3323	likely_benign	0.3295	benign	0.136	Stabilizing	0.992	D	0.552	neutral	None	None	None	None	N
Q/N	0.6899	likely_pathogenic	0.6795	pathogenic	-1.265	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
Q/P	0.9292	likely_pathogenic	0.8908	pathogenic	-0.361	Destabilizing	0.998	D	0.685	prob.neutral	N	0.507883691	None	None	N
Q/R	0.1805	likely_benign	0.1604	benign	-0.777	Destabilizing	0.973	D	0.521	neutral	N	0.447810782	None	None	N
Q/S	0.5728	likely_pathogenic	0.5682	pathogenic	-1.519	Destabilizing	0.995	D	0.495	neutral	None	None	None	None	N
Q/T	0.5378	ambiguous	0.4981	ambiguous	-1.089	Destabilizing	0.878	D	0.604	neutral	None	None	None	None	N
Q/V	0.3686	ambiguous	0.3457	ambiguous	-0.361	Destabilizing	0.846	D	0.603	neutral	None	None	None	None	N
Q/W	0.8154	likely_pathogenic	0.7821	pathogenic	-0.816	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
Q/Y	0.6479	likely_pathogenic	0.6523	pathogenic	-0.407	Destabilizing	0.997	D	0.699	prob.neutral	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.