TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28616	86071;86072;86073	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
N2AB	26975	81148;81149;81150	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
N2A	26048	78367;78368;78369	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
N2B	19551	58876;58877;58878	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
Novex-1	19676	59251;59252;59253	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
Novex-2	19743	59452;59453;59454	chr2:178560286;178560285;178560284	chr2:179425013;179425012;179425011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-96
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.754
• 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/L	rs373942982	None	0.913	N	0.515	0.342	0.517104213562	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs373942982	None	0.913	N	0.515	0.342	0.517104213562	gnomAD-4.0.0	6.57454E-06	None	None	None	None	N	None	2.41324E-05	0	None	0	0	None	0	0	0	0	0
R/Q	rs373942982	0.038	0.997	N	0.564	0.315	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.68E-05	0
R/Q	rs373942982	0.038	0.997	N	0.564	0.315	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	4.41E-05	0	0
R/Q	rs373942982	0.038	0.997	N	0.564	0.315	None	gnomAD-4.0.0	2.23096E-05	None	None	None	None	N	None	4.00502E-05	0	None	0	0	None	0	0	2.37334E-05	1.09789E-05	6.40451E-05
R/W	rs754025981	-0.541	0.999	N	0.619	0.471	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	4.13E-05	2.83E-05	None	0	5.13E-05	None	3.27E-05	None	0	1.56E-05	0
R/W	rs754025981	-0.541	0.999	N	0.619	0.471	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	2.41E-05	6.56E-05	0	0	0	None	0	0	4.41E-05	2.07555E-04	0
R/W	rs754025981	-0.541	0.999	N	0.619	0.471	None	gnomAD-4.0.0	3.53241E-05	None	None	None	None	N	None	4.00555E-05	3.33511E-05	None	0	6.68807E-05	None	0	0	3.81426E-05	2.19597E-05	3.20236E-05

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	0.7229	likely_pathogenic	0.6945	pathogenic	-0.153	Destabilizing	0.916	D	0.535	neutral	None	None	None	None	N
R/C	0.3237	likely_benign	0.3241	benign	-0.325	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
R/D	0.926	likely_pathogenic	0.9208	pathogenic	-0.082	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	N
R/E	0.6707	likely_pathogenic	0.6627	pathogenic	0.016	Stabilizing	0.957	D	0.555	neutral	None	None	None	None	N
R/F	0.7626	likely_pathogenic	0.7621	pathogenic	-0.271	Destabilizing	0.95	D	0.63	neutral	None	None	None	None	N
R/G	0.6112	likely_pathogenic	0.5769	pathogenic	-0.387	Destabilizing	0.977	D	0.489	neutral	N	0.47218216	None	None	N
R/H	0.1836	likely_benign	0.1861	benign	-0.978	Destabilizing	0.975	D	0.583	neutral	None	None	None	None	N
R/I	0.4676	ambiguous	0.4755	ambiguous	0.442	Stabilizing	0.975	D	0.627	neutral	None	None	None	None	N
R/K	0.1625	likely_benign	0.1534	benign	-0.184	Destabilizing	0.901	D	0.483	neutral	None	None	None	None	N
R/L	0.4023	ambiguous	0.4125	ambiguous	0.442	Stabilizing	0.913	D	0.515	neutral	N	0.456894412	None	None	N
R/M	0.4441	ambiguous	0.4643	ambiguous	-0.091	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
R/N	0.8682	likely_pathogenic	0.8586	pathogenic	-0.029	Destabilizing	0.987	D	0.551	neutral	None	None	None	None	N
R/P	0.8877	likely_pathogenic	0.8723	pathogenic	0.265	Stabilizing	0.998	D	0.595	neutral	N	0.484678446	None	None	N
R/Q	0.1649	likely_benign	0.1634	benign	-0.064	Destabilizing	0.997	D	0.564	neutral	N	0.454392825	None	None	N
R/S	0.8195	likely_pathogenic	0.7954	pathogenic	-0.427	Destabilizing	0.987	D	0.515	neutral	None	None	None	None	N
R/T	0.5085	ambiguous	0.4936	ambiguous	-0.169	Destabilizing	0.987	D	0.504	neutral	None	None	None	None	N
R/V	0.5618	ambiguous	0.5687	pathogenic	0.265	Stabilizing	0.975	D	0.57	neutral	None	None	None	None	N
R/W	0.2311	likely_benign	0.2589	benign	-0.281	Destabilizing	0.999	D	0.619	neutral	N	0.479525994	None	None	N
R/Y	0.5889	likely_pathogenic	0.6013	pathogenic	0.115	Stabilizing	0.073	N	0.399	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.