TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18307	55144;55145;55146	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
N2AB	16666	50221;50222;50223	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
N2A	15739	47440;47441;47442	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
N2B	9242	27949;27950;27951	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
Novex-1	9367	28324;28325;28326	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
Novex-2	9434	28525;28526;28527	chr2:178602483;178602482;178602481	chr2:179467210;179467209;179467208
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: Fn3-21
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.097
• 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/H	None	None	1.0	D	0.815	0.732	0.700453235612	gnomAD-4.0.0	1.59536E-06	None	None	None	None	N	None	0	0	None	0	2.79501E-05	None	0	0	0	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	0.9955	likely_pathogenic	0.9975	pathogenic	-3.73	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
Y/C	0.8882	likely_pathogenic	0.9322	pathogenic	-1.847	Destabilizing	1.0	D	0.869	deleterious	D	0.629755114	None	None	N
Y/D	0.9927	likely_pathogenic	0.9956	pathogenic	-3.855	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.64597628	None	None	N
Y/E	0.9984	likely_pathogenic	0.9991	pathogenic	-3.642	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/F	0.3094	likely_benign	0.3817	ambiguous	-1.67	Destabilizing	0.999	D	0.656	neutral	N	0.506040262	None	None	N
Y/G	0.9849	likely_pathogenic	0.9903	pathogenic	-4.112	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9699	likely_pathogenic	0.9831	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.62955331	None	None	N
Y/I	0.9744	likely_pathogenic	0.984	pathogenic	-2.419	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9985	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/L	0.95	likely_pathogenic	0.9631	pathogenic	-2.419	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
Y/M	0.9803	likely_pathogenic	0.9881	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/N	0.9587	likely_pathogenic	0.9729	pathogenic	-3.362	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.64597628	None	None	N
Y/P	0.9989	likely_pathogenic	0.9993	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9985	pathogenic	-3.098	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/R	0.9923	likely_pathogenic	0.994	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/S	0.9821	likely_pathogenic	0.9894	pathogenic	-3.631	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.64597628	None	None	N
Y/T	0.9948	likely_pathogenic	0.9969	pathogenic	-3.306	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/V	0.9585	likely_pathogenic	0.9723	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
Y/W	0.8195	likely_pathogenic	0.8587	pathogenic	-0.863	Destabilizing	1.0	D	0.803	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.