TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8787	26584;26585;26586	chr2:178714415;178714414;178714413	chr2:179579142;179579141;179579140
N2AB	8470	25633;25634;25635	chr2:178714415;178714414;178714413	chr2:179579142;179579141;179579140
N2A	7543	22852;22853;22854	chr2:178714415;178714414;178714413	chr2:179579142;179579141;179579140
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: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-73
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.2777
• 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	rs1365431842	-0.867	0.993	N	0.661	0.537	0.692462537607	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	1.11346E-04	None	0	None	0	0	0
Y/C	rs1365431842	-0.867	0.993	N	0.661	0.537	0.692462537607	gnomAD-4.0.0	2.05272E-06	None	None	None	None	N	None	0	0	None	0	7.55744E-05	None	0	0	0	0	0
Y/F	None	None	None	N	0.281	0.142	0.289847578895	gnomAD-4.0.0	6.8424E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99497E-07	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	0.4075	ambiguous	0.5384	ambiguous	-1.939	Destabilizing	0.706	D	0.637	neutral	None	None	None	None	N
Y/C	0.1294	likely_benign	0.1803	benign	-0.891	Destabilizing	0.993	D	0.661	neutral	N	0.520459716	None	None	N
Y/D	0.2657	likely_benign	0.4106	ambiguous	-0.143	Destabilizing	0.864	D	0.684	prob.neutral	N	0.496822052	None	None	N
Y/E	0.5988	likely_pathogenic	0.7409	pathogenic	-0.056	Destabilizing	0.894	D	0.686	prob.neutral	None	None	None	None	N
Y/F	0.1005	likely_benign	0.1035	benign	-0.726	Destabilizing	None	N	0.281	neutral	N	0.430567108	None	None	N
Y/G	0.3853	ambiguous	0.5159	ambiguous	-2.258	Highly Destabilizing	0.706	D	0.673	neutral	None	None	None	None	N
Y/H	0.1312	likely_benign	0.1726	benign	-0.762	Destabilizing	0.004	N	0.298	neutral	N	0.485972726	None	None	N
Y/I	0.3901	ambiguous	0.4922	ambiguous	-0.994	Destabilizing	0.045	N	0.608	neutral	None	None	None	None	N
Y/K	0.5052	ambiguous	0.6314	pathogenic	-0.923	Destabilizing	0.505	D	0.686	prob.neutral	None	None	None	None	N
Y/L	0.3703	ambiguous	0.4426	ambiguous	-0.994	Destabilizing	0.019	N	0.549	neutral	None	None	None	None	N
Y/M	0.5971	likely_pathogenic	0.6761	pathogenic	-0.79	Destabilizing	0.837	D	0.624	neutral	None	None	None	None	N
Y/N	0.1655	likely_benign	0.2304	benign	-1.231	Destabilizing	0.761	D	0.684	prob.neutral	N	0.499464259	None	None	N
Y/P	0.7933	likely_pathogenic	0.8862	pathogenic	-1.301	Destabilizing	0.981	D	0.685	prob.neutral	None	None	None	None	N
Y/Q	0.3964	ambiguous	0.5206	ambiguous	-1.1	Destabilizing	0.717	D	0.644	neutral	None	None	None	None	N
Y/R	0.3155	likely_benign	0.4209	ambiguous	-0.601	Destabilizing	0.778	D	0.692	prob.neutral	None	None	None	None	N
Y/S	0.1558	likely_benign	0.2245	benign	-1.837	Destabilizing	0.645	D	0.68	prob.neutral	N	0.517319301	None	None	N
Y/T	0.319	likely_benign	0.4224	ambiguous	-1.649	Destabilizing	0.945	D	0.684	prob.neutral	None	None	None	None	N
Y/V	0.3147	likely_benign	0.3953	ambiguous	-1.301	Destabilizing	0.706	D	0.549	neutral	None	None	None	None	N
Y/W	0.3611	ambiguous	0.4102	ambiguous	-0.378	Destabilizing	0.967	D	0.616	neutral	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.