TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2666	8221;8222;8223	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
N2AB	2666	8221;8222;8223	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
N2A	2666	8221;8222;8223	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
N2B	2620	8083;8084;8085	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
Novex-1	2620	8083;8084;8085	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
Novex-2	2620	8083;8084;8085	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056
Novex-3	2666	8221;8222;8223	chr2:178771331;178771330;178771329	chr2:179636058;179636057;179636056

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-16
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.2522
• 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/G	rs2091455237	None	None	N	0.203	0.171	0.408988072059	gnomAD-4.0.0	2.73634E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5972E-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	0.2226	likely_benign	0.2464	benign	-1.256	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	N
R/C	0.1494	likely_benign	0.1631	benign	-1.252	Destabilizing	0.864	D	0.334	neutral	None	None	None	None	N
R/D	0.4516	ambiguous	0.4663	ambiguous	-0.104	Destabilizing	0.072	N	0.369	neutral	None	None	None	None	N
R/E	0.2165	likely_benign	0.2286	benign	0.048	Stabilizing	0.016	N	0.281	neutral	None	None	None	None	N
R/F	0.2902	likely_benign	0.3061	benign	-0.922	Destabilizing	0.356	N	0.366	neutral	None	None	None	None	N
R/G	0.1849	likely_benign	0.1982	benign	-1.587	Destabilizing	None	N	0.203	neutral	N	0.504113891	None	None	N
R/H	0.0822	likely_benign	0.0845	benign	-1.617	Destabilizing	None	N	0.199	neutral	None	None	None	None	N
R/I	0.1095	likely_benign	0.1153	benign	-0.345	Destabilizing	0.029	N	0.398	neutral	N	0.509584452	None	None	N
R/K	0.0771	likely_benign	0.0812	benign	-1.131	Destabilizing	None	N	0.121	neutral	N	0.440852345	None	None	N
R/L	0.1384	likely_benign	0.1443	benign	-0.345	Destabilizing	0.016	N	0.369	neutral	None	None	None	None	N
R/M	0.1548	likely_benign	0.1667	benign	-0.706	Destabilizing	0.356	N	0.348	neutral	None	None	None	None	N
R/N	0.3081	likely_benign	0.3371	benign	-0.637	Destabilizing	0.072	N	0.246	neutral	None	None	None	None	N
R/P	0.7544	likely_pathogenic	0.6918	pathogenic	-0.63	Destabilizing	0.136	N	0.389	neutral	None	None	None	None	N
R/Q	0.0851	likely_benign	0.0879	benign	-0.778	Destabilizing	0.038	N	0.325	neutral	None	None	None	None	N
R/S	0.2473	likely_benign	0.2703	benign	-1.588	Destabilizing	0.012	N	0.357	neutral	N	0.499216629	None	None	N
R/T	0.1072	likely_benign	0.1184	benign	-1.239	Destabilizing	0.055	N	0.361	neutral	N	0.503451382	None	None	N
R/V	0.1682	likely_benign	0.1782	benign	-0.63	Destabilizing	None	N	0.253	neutral	None	None	None	None	N
R/W	0.1504	likely_benign	0.148	benign	-0.44	Destabilizing	0.864	D	0.362	neutral	None	None	None	None	N
R/Y	0.2415	likely_benign	0.251	benign	-0.211	Destabilizing	0.214	N	0.373	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.