TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8620	26083;26084;26085	chr2:178715556;178715555;178715554	chr2:179580283;179580282;179580281
N2AB	8303	25132;25133;25134	chr2:178715556;178715555;178715554	chr2:179580283;179580282;179580281
N2A	7376	22351;22352;22353	chr2:178715556;178715555;178715554	chr2:179580283;179580282;179580281
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-71
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.0855
• 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	0.873	0.872	0.87617659604	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-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	0.9881	likely_pathogenic	0.9713	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/C	0.8165	likely_pathogenic	0.6621	pathogenic	-2.018	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.645297633	None	None	N
Y/D	0.9959	likely_pathogenic	0.9897	pathogenic	-3.079	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.661316994	None	None	N
Y/E	0.9985	likely_pathogenic	0.996	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/F	0.0899	likely_benign	0.0789	benign	-0.924	Destabilizing	0.999	D	0.676	prob.neutral	D	0.551372749	None	None	N
Y/G	0.9884	likely_pathogenic	0.9733	pathogenic	-2.898	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/H	0.9488	likely_pathogenic	0.8874	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.783	deleterious	D	0.66111519	None	None	N
Y/I	0.6536	likely_pathogenic	0.558	ambiguous	-0.934	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
Y/K	0.9975	likely_pathogenic	0.9937	pathogenic	-1.944	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/L	0.6955	likely_pathogenic	0.6096	pathogenic	-0.934	Destabilizing	0.997	D	0.78	deleterious	None	None	None	None	N
Y/M	0.9081	likely_pathogenic	0.8553	pathogenic	-1.173	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/N	0.9741	likely_pathogenic	0.9392	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.661316994	None	None	N
Y/P	0.9985	likely_pathogenic	0.9969	pathogenic	-1.454	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/Q	0.997	likely_pathogenic	0.9916	pathogenic	-2.417	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.991	likely_pathogenic	0.9792	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/S	0.9761	likely_pathogenic	0.9416	pathogenic	-3.171	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.661316994	None	None	N
Y/T	0.9835	likely_pathogenic	0.9604	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.6207	likely_pathogenic	0.5037	ambiguous	-1.454	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/W	0.7779	likely_pathogenic	0.7212	pathogenic	-0.3	Destabilizing	1.0	D	0.779	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.