TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28125	84598;84599;84600	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
N2AB	26484	79675;79676;79677	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
N2A	25557	76894;76895;76896	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
N2B	19060	57403;57404;57405	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
Novex-1	19185	57778;57779;57780	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
Novex-2	19252	57979;57980;57981	chr2:178561759;178561758;178561757	chr2:179426486;179426485;179426484
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: Fn3-92
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0863
• 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	rs763653948	-2.163	1.0	D	0.866	0.864	0.872586506267	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/C	rs763653948	-2.163	1.0	D	0.866	0.864	0.872586506267	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85887E-06	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
Y/A	0.9957	likely_pathogenic	0.9944	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/C	0.9507	likely_pathogenic	0.9403	pathogenic	-1.866	Destabilizing	1.0	D	0.866	deleterious	D	0.682454645	None	None	N
Y/D	0.9934	likely_pathogenic	0.9887	pathogenic	-3.375	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.698474006	None	None	N
Y/E	0.998	likely_pathogenic	0.9967	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/F	0.3119	likely_benign	0.2733	benign	-1.092	Destabilizing	0.999	D	0.763	deleterious	D	0.6353663	None	None	N
Y/G	0.9827	likely_pathogenic	0.9815	pathogenic	-3.553	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/H	0.969	likely_pathogenic	0.9505	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.698474006	None	None	N
Y/I	0.9714	likely_pathogenic	0.9561	pathogenic	-1.7	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/K	0.9976	likely_pathogenic	0.9958	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.9559	likely_pathogenic	0.9477	pathogenic	-1.7	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
Y/M	0.9819	likely_pathogenic	0.9734	pathogenic	-1.556	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/N	0.9584	likely_pathogenic	0.9213	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.698272202	None	None	N
Y/P	0.9993	likely_pathogenic	0.999	pathogenic	-2.191	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/Q	0.997	likely_pathogenic	0.9947	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9951	likely_pathogenic	0.9925	pathogenic	-1.873	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/S	0.985	likely_pathogenic	0.9783	pathogenic	-3.264	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.698474006	None	None	N
Y/T	0.9945	likely_pathogenic	0.9918	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/V	0.9555	likely_pathogenic	0.9408	pathogenic	-2.191	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/W	0.8894	likely_pathogenic	0.8713	pathogenic	-0.335	Destabilizing	1.0	D	0.818	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.