TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33448	100567;100568;100569	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
N2AB	31807	95644;95645;95646	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
N2A	30880	92863;92864;92865	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
N2B	24383	73372;73373;73374	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
Novex-1	24508	73747;73748;73749	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
Novex-2	24575	73948;73949;73950	chr2:178536405;178536404;178536403	chr2:179401132;179401131;179401130
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Fn3-131
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.5296
• 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/P	rs1315622743	None	0.996	N	0.63	0.345	0.313210971179	gnomAD-4.0.0	2.7372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59811E-06	0	0
R/Q	rs1315622743	None	0.983	N	0.496	0.149	0.119812018005	gnomAD-4.0.0	9.58021E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.16939E-05	1.15947E-05	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	0.3695	ambiguous	0.3939	ambiguous	0.008	Stabilizing	0.737	D	0.421	neutral	None	None	None	None	N
R/C	0.1849	likely_benign	0.176	benign	-0.066	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	N
R/D	0.6322	likely_pathogenic	0.663	pathogenic	0.015	Stabilizing	0.932	D	0.593	neutral	None	None	None	None	N
R/E	0.3878	ambiguous	0.4112	ambiguous	0.099	Stabilizing	0.872	D	0.399	neutral	None	None	None	None	N
R/F	0.5319	ambiguous	0.5474	ambiguous	-0.064	Destabilizing	0.96	D	0.6	neutral	None	None	None	None	N
R/G	0.2329	likely_benign	0.2484	benign	-0.228	Destabilizing	0.963	D	0.574	neutral	N	0.442786178	None	None	N
R/H	0.1081	likely_benign	0.0952	benign	-0.697	Destabilizing	0.021	N	0.321	neutral	None	None	None	None	N
R/I	0.3441	ambiguous	0.3517	ambiguous	0.605	Stabilizing	0.773	D	0.529	neutral	None	None	None	None	N
R/K	0.1217	likely_benign	0.1107	benign	-0.04	Destabilizing	0.737	D	0.431	neutral	None	None	None	None	N
R/L	0.2627	likely_benign	0.2722	benign	0.605	Stabilizing	0.017	N	0.415	neutral	N	0.438015076	None	None	N
R/M	0.3809	ambiguous	0.3854	ambiguous	0.123	Stabilizing	0.96	D	0.566	neutral	None	None	None	None	N
R/N	0.4709	ambiguous	0.4967	ambiguous	0.272	Stabilizing	0.872	D	0.419	neutral	None	None	None	None	N
R/P	0.4267	ambiguous	0.4686	ambiguous	0.428	Stabilizing	0.996	D	0.63	neutral	N	0.422333548	None	None	N
R/Q	0.1201	likely_benign	0.1166	benign	0.17	Stabilizing	0.983	D	0.496	neutral	N	0.450944301	None	None	N
R/S	0.4144	ambiguous	0.4491	ambiguous	-0.13	Destabilizing	0.773	D	0.481	neutral	None	None	None	None	N
R/T	0.2318	likely_benign	0.2472	benign	0.101	Stabilizing	0.083	N	0.332	neutral	None	None	None	None	N
R/V	0.411	ambiguous	0.4195	ambiguous	0.428	Stabilizing	0.083	N	0.479	neutral	None	None	None	None	N
R/W	0.2288	likely_benign	0.2262	benign	-0.04	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
R/Y	0.4274	ambiguous	0.4117	ambiguous	0.345	Stabilizing	0.96	D	0.631	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.