TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19254	57985;57986;57987	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
N2AB	17613	53062;53063;53064	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
N2A	16686	50281;50282;50283	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
N2B	10189	30790;30791;30792	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
Novex-1	10314	31165;31166;31167	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
Novex-2	10381	31366;31367;31368	chr2:178595594;178595593;178595592	chr2:179460321;179460320;179460319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-27
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0939
• 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	None	None	1.0	D	0.875	0.899	0.918309405657	gnomAD-4.0.0	1.66373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.986E-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	0.9888	likely_pathogenic	0.9933	pathogenic	-3.323	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/C	0.7633	likely_pathogenic	0.852	pathogenic	-1.948	Destabilizing	1.0	D	0.873	deleterious	D	0.661559827	None	None	N
Y/D	0.9946	likely_pathogenic	0.9966	pathogenic	-3.618	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.661559827	None	None	N
Y/E	0.9986	likely_pathogenic	0.9991	pathogenic	-3.405	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/F	0.1717	likely_benign	0.1899	benign	-1.29	Destabilizing	0.999	D	0.745	deleterious	D	0.643724227	None	None	N
Y/G	0.9827	likely_pathogenic	0.9878	pathogenic	-3.744	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.927	likely_pathogenic	0.9567	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.661559827	None	None	N
Y/I	0.9409	likely_pathogenic	0.9615	pathogenic	-1.913	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9992	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/L	0.9164	likely_pathogenic	0.9402	pathogenic	-1.913	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/M	0.973	likely_pathogenic	0.9799	pathogenic	-1.606	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9543	likely_pathogenic	0.9691	pathogenic	-3.324	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.661358022	None	None	N
Y/P	0.9979	likely_pathogenic	0.9986	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
Y/Q	0.9963	likely_pathogenic	0.998	pathogenic	-3.058	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/R	0.9927	likely_pathogenic	0.9962	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/S	0.9469	likely_pathogenic	0.9687	pathogenic	-3.666	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.636021715	None	None	N
Y/T	0.9813	likely_pathogenic	0.989	pathogenic	-3.333	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/V	0.8861	likely_pathogenic	0.9191	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
Y/W	0.6357	likely_pathogenic	0.6995	pathogenic	-0.563	Destabilizing	1.0	D	0.808	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.