TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6282	19069;19070;19071	chr2:178729312;178729311;178729310	chr2:179594039;179594038;179594037
N2AB	5965	18118;18119;18120	chr2:178729312;178729311;178729310	chr2:179594039;179594038;179594037
N2A	5038	15337;15338;15339	chr2:178729312;178729311;178729310	chr2:179594039;179594038;179594037
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: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-46
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1157
• 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/F	rs2079961331	None	0.484	N	0.82	0.339	0.764433835033	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
C/F	rs2079961331	None	0.484	N	0.82	0.339	0.764433835033	gnomAD-4.0.0	2.0299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40987E-06	0	0
C/R	None	None	0.317	D	0.835	0.301	0.649823028507	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
C/A	0.2748	likely_benign	0.2905	benign	-1.939	Destabilizing	0.035	N	0.509	neutral	None	None	None	None	N
C/D	0.7822	likely_pathogenic	0.7419	pathogenic	-0.404	Destabilizing	0.235	N	0.811	deleterious	None	None	None	None	N
C/E	0.9042	likely_pathogenic	0.8732	pathogenic	-0.297	Destabilizing	0.235	N	0.811	deleterious	None	None	None	None	N
C/F	0.4053	ambiguous	0.322	benign	-1.274	Destabilizing	0.484	N	0.82	deleterious	N	0.501265824	None	None	N
C/G	0.1583	likely_benign	0.1701	benign	-2.252	Highly Destabilizing	0.062	N	0.789	deleterious	N	0.487934509	None	None	N
C/H	0.6818	likely_pathogenic	0.5977	pathogenic	-2.158	Highly Destabilizing	0.824	D	0.817	deleterious	None	None	None	None	N
C/I	0.5743	likely_pathogenic	0.5157	ambiguous	-1.125	Destabilizing	0.38	N	0.818	deleterious	None	None	None	None	N
C/K	0.8977	likely_pathogenic	0.8429	pathogenic	-1.026	Destabilizing	0.081	N	0.813	deleterious	None	None	None	None	N
C/L	0.5636	ambiguous	0.4976	ambiguous	-1.125	Destabilizing	0.149	N	0.772	deleterious	None	None	None	None	N
C/M	0.6885	likely_pathogenic	0.6784	pathogenic	-0.142	Destabilizing	0.935	D	0.791	deleterious	None	None	None	None	N
C/N	0.5155	ambiguous	0.5295	ambiguous	-1.002	Destabilizing	0.235	N	0.811	deleterious	None	None	None	None	N
C/P	0.9814	likely_pathogenic	0.9765	pathogenic	-1.371	Destabilizing	0.38	N	0.829	deleterious	None	None	None	None	N
C/Q	0.7793	likely_pathogenic	0.7077	pathogenic	-0.918	Destabilizing	0.38	N	0.836	deleterious	None	None	None	None	N
C/R	0.686	likely_pathogenic	0.5382	ambiguous	-0.869	Destabilizing	0.317	N	0.835	deleterious	D	0.532846113	None	None	N
C/S	0.1277	likely_benign	0.1498	benign	-1.598	Destabilizing	None	N	0.431	neutral	N	0.442666826	None	None	N
C/T	0.2515	likely_benign	0.2874	benign	-1.304	Destabilizing	0.081	N	0.77	deleterious	None	None	None	None	N
C/V	0.4263	ambiguous	0.3964	ambiguous	-1.371	Destabilizing	0.149	N	0.785	deleterious	None	None	None	None	N
C/W	0.7811	likely_pathogenic	0.6897	pathogenic	-1.22	Destabilizing	0.915	D	0.778	deleterious	N	0.506799232	None	None	N
C/Y	0.5732	likely_pathogenic	0.4662	ambiguous	-1.234	Destabilizing	0.484	N	0.801	deleterious	N	0.497898462	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.