TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16329	49210;49211;49212	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
N2AB	14688	44287;44288;44289	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
N2A	13761	41506;41507;41508	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
N2B	7264	22015;22016;22017	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
Novex-1	7389	22390;22391;22392	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
Novex-2	7456	22591;22592;22593	chr2:178614529;178614528;178614527	chr2:179479256;179479255;179479254
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-110
• Domain position: 68
• Structural Position: 154
• Q(SASA): 0.1437
• 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	rs1456507512	-0.707	1.0	D	0.823	0.855	0.896210243133	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	9.99E-05	0	None	0	None	0	0	0
Y/C	rs1456507512	-0.707	1.0	D	0.823	0.855	0.896210243133	gnomAD-4.0.0	2.73902E-06	None	None	None	None	N	None	0	0	None	7.66754E-05	0	None	0	0	8.99892E-07	0	1.65854E-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	0.9985	likely_pathogenic	0.9985	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/C	0.963	likely_pathogenic	0.9643	pathogenic	-1.688	Destabilizing	1.0	D	0.823	deleterious	D	0.830037856	None	None	N
Y/D	0.999	likely_pathogenic	0.9989	pathogenic	-2.174	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.830037856	None	None	N
Y/E	0.9998	likely_pathogenic	0.9997	pathogenic	-1.927	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/F	0.2304	likely_benign	0.2316	benign	-0.62	Destabilizing	0.999	D	0.718	prob.delet.	D	0.715713032	None	None	N
Y/G	0.9973	likely_pathogenic	0.9972	pathogenic	-2.613	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/H	0.9902	likely_pathogenic	0.9888	pathogenic	-1.7	Destabilizing	1.0	D	0.795	deleterious	D	0.830682456	None	None	N
Y/I	0.9738	likely_pathogenic	0.9745	pathogenic	-0.679	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/K	0.9997	likely_pathogenic	0.9997	pathogenic	-1.779	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/L	0.9426	likely_pathogenic	0.943	pathogenic	-0.679	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
Y/M	0.9879	likely_pathogenic	0.988	pathogenic	-0.806	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/N	0.9946	likely_pathogenic	0.994	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.830037856	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-1.184	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/Q	0.9997	likely_pathogenic	0.9996	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/R	0.9986	likely_pathogenic	0.9985	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/S	0.9957	likely_pathogenic	0.9952	pathogenic	-3.079	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.830037856	None	None	N
Y/T	0.9983	likely_pathogenic	0.9982	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/V	0.9557	likely_pathogenic	0.9571	pathogenic	-1.184	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/W	0.7636	likely_pathogenic	0.7772	pathogenic	0.039	Stabilizing	1.0	D	0.791	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.