TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17742	53449;53450;53451	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
N2AB	16101	48526;48527;48528	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
N2A	15174	45745;45746;45747	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
N2B	8677	26254;26255;26256	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
Novex-1	8802	26629;26630;26631	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
Novex-2	8869	26830;26831;26832	chr2:178607464;178607463;178607462	chr2:179472191;179472190;179472189
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-113
• Domain position: 66
• Structural Position: 154
• Q(SASA): 0.1638
• 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/C	None	None	1.0	D	0.819	0.821	0.892054323885	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02773E-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	0.9978	likely_pathogenic	0.997	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/C	0.9682	likely_pathogenic	0.9525	pathogenic	-1.538	Destabilizing	1.0	D	0.819	deleterious	D	0.650869585	None	None	N
Y/D	0.9979	likely_pathogenic	0.9969	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.650869585	None	None	N
Y/E	0.9992	likely_pathogenic	0.9989	pathogenic	-2.61	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/F	0.2265	likely_benign	0.1838	benign	-0.673	Destabilizing	0.999	D	0.707	prob.neutral	D	0.603609795	None	None	N
Y/G	0.9949	likely_pathogenic	0.9931	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/H	0.9819	likely_pathogenic	0.9732	pathogenic	-1.939	Destabilizing	1.0	D	0.793	deleterious	D	0.634648419	None	None	N
Y/I	0.9496	likely_pathogenic	0.9333	pathogenic	-0.617	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9985	pathogenic	-1.894	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/L	0.9168	likely_pathogenic	0.9022	pathogenic	-0.617	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
Y/M	0.9818	likely_pathogenic	0.9759	pathogenic	-0.706	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/N	0.9906	likely_pathogenic	0.9863	pathogenic	-2.852	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.650869585	None	None	N
Y/P	0.9991	likely_pathogenic	0.9988	pathogenic	-1.125	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9987	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/R	0.9965	likely_pathogenic	0.9952	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/S	0.9957	likely_pathogenic	0.9938	pathogenic	-3.132	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.650869585	None	None	N
Y/T	0.9976	likely_pathogenic	0.9966	pathogenic	-2.734	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/V	0.946	likely_pathogenic	0.928	pathogenic	-1.125	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/W	0.7945	likely_pathogenic	0.7486	pathogenic	-0.092	Destabilizing	1.0	D	0.783	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.