TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8684	26275;26276;26277	chr2:178715136;178715135;178715134	chr2:179579863;179579862;179579861
N2AB	8367	25324;25325;25326	chr2:178715136;178715135;178715134	chr2:179579863;179579862;179579861
N2A	7440	22543;22544;22545	chr2:178715136;178715135;178715134	chr2:179579863;179579862;179579861
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-72
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5249
• 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
R/M	rs1185236077	-0.194	0.054	N	0.199	0.187	0.304435445954	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
R/M	rs1185236077	-0.194	0.054	N	0.199	0.187	0.304435445954	gnomAD-4.0.0	1.36848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79904E-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
R/A	0.5462	ambiguous	0.5713	pathogenic	0.051	Stabilizing	0.154	N	0.24	neutral	None	None	None	None	N
R/C	0.2443	likely_benign	0.2734	benign	-0.311	Destabilizing	0.994	D	0.271	neutral	None	None	None	None	N
R/D	0.8321	likely_pathogenic	0.852	pathogenic	-0.321	Destabilizing	0.669	D	0.388	neutral	None	None	None	None	N
R/E	0.5951	likely_pathogenic	0.6068	pathogenic	-0.279	Destabilizing	0.111	N	0.265	neutral	None	None	None	None	N
R/F	0.5855	likely_pathogenic	0.5994	pathogenic	-0.286	Destabilizing	0.738	D	0.32	neutral	None	None	None	None	N
R/G	0.3826	ambiguous	0.413	ambiguous	-0.083	Destabilizing	0.386	N	0.327	neutral	N	0.515012501	None	None	N
R/H	0.1155	likely_benign	0.1257	benign	-0.571	Destabilizing	0.948	D	0.336	neutral	None	None	None	None	N
R/I	0.3329	likely_benign	0.3648	ambiguous	0.356	Stabilizing	0.296	N	0.363	neutral	None	None	None	None	N
R/K	0.1015	likely_benign	0.1074	benign	-0.195	Destabilizing	None	N	0.142	neutral	N	0.460329867	None	None	N
R/L	0.2992	likely_benign	0.3344	benign	0.356	Stabilizing	0.148	N	0.278	neutral	None	None	None	None	N
R/M	0.378	ambiguous	0.4099	ambiguous	-0.116	Destabilizing	0.054	N	0.199	neutral	N	0.489722162	None	None	N
R/N	0.7026	likely_pathogenic	0.7336	pathogenic	-0.165	Destabilizing	0.669	D	0.289	neutral	None	None	None	None	N
R/P	0.5931	likely_pathogenic	0.6024	pathogenic	0.272	Stabilizing	0.804	D	0.375	neutral	None	None	None	None	N
R/Q	0.1327	likely_benign	0.1437	benign	-0.175	Destabilizing	0.599	D	0.309	neutral	None	None	None	None	N
R/S	0.641	likely_pathogenic	0.6648	pathogenic	-0.318	Destabilizing	0.056	N	0.179	neutral	N	0.472605731	None	None	N
R/T	0.3888	ambiguous	0.4237	ambiguous	-0.172	Destabilizing	0.02	N	0.163	neutral	N	0.503832715	None	None	N
R/V	0.4212	ambiguous	0.45	ambiguous	0.272	Stabilizing	0.008	N	0.23	neutral	None	None	None	None	N
R/W	0.1815	likely_benign	0.1938	benign	-0.492	Destabilizing	0.995	D	0.279	neutral	N	0.509890332	None	None	N
R/Y	0.4368	ambiguous	0.4628	ambiguous	-0.081	Destabilizing	0.946	D	0.323	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.