TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19855	59788;59789;59790	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
N2AB	18214	54865;54866;54867	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
N2A	17287	52084;52085;52086	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
N2B	10790	32593;32594;32595	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
Novex-1	10915	32968;32969;32970	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
Novex-2	10982	33169;33170;33171	chr2:178592442;178592441;178592440	chr2:179457169;179457168;179457167
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-119
• Domain position: 66
• Structural Position: 154
• Q(SASA): 0.1436
• 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
Y/N	rs779395388	-3.275	1.0	D	0.887	0.877	0.886385070211	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
Y/N	rs779395388	-3.275	1.0	D	0.887	0.877	0.886385070211	gnomAD-4.0.0	6.36787E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57839E-06	0	3.02499E-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
Y/A	0.9979	likely_pathogenic	0.9984	pathogenic	-2.986	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/C	0.9573	likely_pathogenic	0.9654	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.645529798	None	None	N
Y/D	0.9982	likely_pathogenic	0.9987	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.645529798	None	None	N
Y/E	0.9995	likely_pathogenic	0.9996	pathogenic	-3.183	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.1825	likely_benign	0.1649	benign	-1.137	Destabilizing	0.999	D	0.703	prob.neutral	D	0.577607354	None	None	N
Y/G	0.996	likely_pathogenic	0.9969	pathogenic	-3.454	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/H	0.9722	likely_pathogenic	0.9785	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.808	deleterious	D	0.645327993	None	None	N
Y/I	0.957	likely_pathogenic	0.9625	pathogenic	-1.428	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9995	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.9221	likely_pathogenic	0.9227	pathogenic	-1.428	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
Y/M	0.9897	likely_pathogenic	0.9901	pathogenic	-1.412	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9933	likely_pathogenic	0.9949	pathogenic	-3.333	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.645529798	None	None	N
Y/P	0.9984	likely_pathogenic	0.999	pathogenic	-1.965	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9993	pathogenic	-2.942	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/R	0.9957	likely_pathogenic	0.997	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/S	0.9922	likely_pathogenic	0.9943	pathogenic	-3.707	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.645529798	None	None	N
Y/T	0.9967	likely_pathogenic	0.9977	pathogenic	-3.318	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9539	likely_pathogenic	0.9593	pathogenic	-1.965	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/W	0.6865	likely_pathogenic	0.7107	pathogenic	-0.434	Destabilizing	1.0	D	0.799	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.