TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8031	24316;24317;24318	chr2:178719299;178719298;178719297	chr2:179584026;179584025;179584024
N2AB	7714	23365;23366;23367	chr2:178719299;178719298;178719297	chr2:179584026;179584025;179584024
N2A	6787	20584;20585;20586	chr2:178719299;178719298;178719297	chr2:179584026;179584025;179584024
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-65
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2097
• 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
C/Y	rs2077976693	None	None	N	0.34	0.234	0.414798848334	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	2.51902E-05	None	0	0	8.9948E-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
C/A	0.2489	likely_benign	0.2973	benign	-1.374	Destabilizing	0.048	N	0.338	neutral	None	None	None	None	N
C/D	0.3795	ambiguous	0.4458	ambiguous	-0.53	Destabilizing	0.364	N	0.616	neutral	None	None	None	None	N
C/E	0.4274	ambiguous	0.504	ambiguous	-0.452	Destabilizing	0.104	N	0.581	neutral	None	None	None	None	N
C/F	0.0744	likely_benign	0.0824	benign	-1.168	Destabilizing	0.042	N	0.531	neutral	N	0.403724436	None	None	N
C/G	0.1131	likely_benign	0.1362	benign	-1.637	Destabilizing	0.151	N	0.559	neutral	N	0.450075588	None	None	N
C/H	0.133	likely_benign	0.1527	benign	-1.988	Destabilizing	None	N	0.439	neutral	None	None	None	None	N
C/I	0.22	likely_benign	0.2488	benign	-0.725	Destabilizing	0.22	N	0.576	neutral	None	None	None	None	N
C/K	0.3379	likely_benign	0.3979	ambiguous	-0.587	Destabilizing	0.22	N	0.605	neutral	None	None	None	None	N
C/L	0.2106	likely_benign	0.2381	benign	-0.725	Destabilizing	0.025	N	0.439	neutral	None	None	None	None	N
C/M	0.3866	ambiguous	0.4346	ambiguous	-0.118	Destabilizing	0.859	D	0.642	neutral	None	None	None	None	N
C/N	0.2176	likely_benign	0.2603	benign	-0.586	Destabilizing	0.22	N	0.605	neutral	None	None	None	None	N
C/P	0.7043	likely_pathogenic	0.7858	pathogenic	-0.915	Destabilizing	0.635	D	0.675	neutral	None	None	None	None	N
C/Q	0.2359	likely_benign	0.276	benign	-0.586	Destabilizing	0.364	N	0.655	neutral	None	None	None	None	N
C/R	0.1314	likely_benign	0.1581	benign	-0.592	Destabilizing	0.175	N	0.631	neutral	N	0.451595741	None	None	N
C/S	0.1577	likely_benign	0.1872	benign	-1.001	Destabilizing	0.081	N	0.513	neutral	N	0.461658019	None	None	N
C/T	0.2564	likely_benign	0.298	benign	-0.753	Destabilizing	0.191	N	0.536	neutral	None	None	None	None	N
C/V	0.2203	likely_benign	0.2432	benign	-0.915	Destabilizing	0.104	N	0.504	neutral	None	None	None	None	N
C/W	0.1688	likely_benign	0.1764	benign	-1.231	Destabilizing	0.602	D	0.637	neutral	N	0.475550036	None	None	N
C/Y	0.0594	likely_benign	0.0644	benign	-1.082	Destabilizing	None	N	0.34	neutral	N	0.326533089	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.