TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2670	8233;8234;8235	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
N2AB	2670	8233;8234;8235	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
N2A	2670	8233;8234;8235	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
N2B	2624	8095;8096;8097	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
Novex-1	2624	8095;8096;8097	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
Novex-2	2624	8095;8096;8097	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044
Novex-3	2670	8233;8234;8235	chr2:178771319;178771318;178771317	chr2:179636046;179636045;179636044

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-16
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.5304
• 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
D/N	rs1344075805	None	0.015	N	0.173	0.2	0.264547087235	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	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
D/A	0.1376	likely_benign	0.1372	benign	-0.441	Destabilizing	0.193	N	0.31	neutral	D	0.586286171	None	None	N
D/C	0.526	ambiguous	0.4917	ambiguous	-0.051	Destabilizing	0.981	D	0.458	neutral	None	None	None	None	N
D/E	0.1498	likely_benign	0.1492	benign	-0.389	Destabilizing	0.001	N	0.193	neutral	N	0.481147208	None	None	N
D/F	0.4473	ambiguous	0.4206	ambiguous	-0.349	Destabilizing	0.818	D	0.421	neutral	None	None	None	None	N
D/G	0.1862	likely_benign	0.1845	benign	-0.652	Destabilizing	0.324	N	0.292	neutral	D	0.577469115	None	None	N
D/H	0.2182	likely_benign	0.1992	benign	-0.294	Destabilizing	0.773	D	0.319	neutral	D	0.619528616	None	None	N
D/I	0.2094	likely_benign	0.2053	benign	0.072	Stabilizing	0.019	N	0.309	neutral	None	None	None	None	N
D/K	0.2401	likely_benign	0.2326	benign	0.188	Stabilizing	0.019	N	0.213	neutral	None	None	None	None	N
D/L	0.2742	likely_benign	0.2598	benign	0.072	Stabilizing	0.241	N	0.369	neutral	None	None	None	None	N
D/M	0.481	ambiguous	0.4664	ambiguous	0.286	Stabilizing	0.944	D	0.419	neutral	None	None	None	None	N
D/N	0.0871	likely_benign	0.0847	benign	-0.14	Destabilizing	0.015	N	0.173	neutral	N	0.501928201	None	None	N
D/P	0.8603	likely_pathogenic	0.8359	pathogenic	-0.077	Destabilizing	0.818	D	0.333	neutral	None	None	None	None	N
D/Q	0.2633	likely_benign	0.2582	benign	-0.11	Destabilizing	0.527	D	0.291	neutral	None	None	None	None	N
D/R	0.2786	likely_benign	0.2617	benign	0.332	Stabilizing	0.527	D	0.395	neutral	None	None	None	None	N
D/S	0.1075	likely_benign	0.107	benign	-0.257	Destabilizing	0.241	N	0.233	neutral	None	None	None	None	N
D/T	0.1784	likely_benign	0.1785	benign	-0.091	Destabilizing	0.388	N	0.319	neutral	None	None	None	None	N
D/V	0.1352	likely_benign	0.1296	benign	-0.077	Destabilizing	0.001	N	0.269	neutral	D	0.534816911	None	None	N
D/W	0.8085	likely_pathogenic	0.7855	pathogenic	-0.187	Destabilizing	0.981	D	0.529	neutral	None	None	None	None	N
D/Y	0.1874	likely_benign	0.1695	benign	-0.111	Destabilizing	0.912	D	0.42	neutral	D	0.643145442	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.