TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17717	53374;53375;53376	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
N2AB	16076	48451;48452;48453	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
N2A	15149	45670;45671;45672	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
N2B	8652	26179;26180;26181	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
Novex-1	8777	26554;26555;26556	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
Novex-2	8844	26755;26756;26757	chr2:178607539;178607538;178607537	chr2:179472266;179472265;179472264
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-113
• Domain position: 41
• Structural Position: 115
• Q(SASA): 0.2983
• 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/C	rs369001587	-0.718	1.0	N	0.604	0.371	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	6.54E-05	None	0	8.91E-06	0
R/C	rs369001587	-0.718	1.0	N	0.604	0.371	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs369001587	-0.718	1.0	N	0.604	0.371	None	gnomAD-4.0.0	7.43944E-06	None	None	None	None	N	None	0	0	None	0	0	None	4.68765E-05	0	3.39165E-06	4.39242E-05	1.60215E-05
R/H	rs757018821	-1.571	0.997	N	0.406	0.334	0.262175524916	gnomAD-2.1.1	5.72E-05	None	None	None	None	N	None	2.48242E-04	1.13116E-04	None	0	0	None	1.30719E-04	None	0	1.57E-05	0
R/H	rs757018821	-1.571	0.997	N	0.406	0.334	0.262175524916	gnomAD-3.1.2	6.58E-05	None	None	None	None	N	None	2.17402E-04	0	0	0	0	None	0	0	0	2.07039E-04	0
R/H	rs757018821	-1.571	0.997	N	0.406	0.334	0.262175524916	gnomAD-4.0.0	2.54175E-05	None	None	None	None	N	None	2.00476E-04	5.003E-05	None	0	2.23095E-05	None	0	0	4.23954E-06	1.53725E-04	4.806E-05
R/P	rs757018821	-0.22	0.994	N	0.477	0.383	0.406120066682	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	0	0	None	0	1.02659E-04	None	0	None	0	0	0
R/P	rs757018821	-0.22	0.994	N	0.477	0.383	0.406120066682	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94704E-04	None	0	0	0	0	0
R/P	rs757018821	-0.22	0.994	N	0.477	0.383	0.406120066682	gnomAD-4.0.0	1.23988E-06	None	None	None	None	N	None	0	0	None	0	4.4619E-05	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
R/A	0.7079	likely_pathogenic	0.7942	pathogenic	-0.686	Destabilizing	0.919	D	0.375	neutral	None	None	None	None	N
R/C	0.298	likely_benign	0.4633	ambiguous	-0.532	Destabilizing	1.0	D	0.604	neutral	N	0.504874134	None	None	N
R/D	0.8386	likely_pathogenic	0.8761	pathogenic	0.074	Stabilizing	0.851	D	0.449	neutral	None	None	None	None	N
R/E	0.6537	likely_pathogenic	0.723	pathogenic	0.202	Stabilizing	0.851	D	0.364	neutral	None	None	None	None	N
R/F	0.8522	likely_pathogenic	0.9139	pathogenic	-0.512	Destabilizing	0.996	D	0.57	neutral	None	None	None	None	N
R/G	0.6195	likely_pathogenic	0.735	pathogenic	-1.007	Destabilizing	0.956	D	0.421	neutral	N	0.470018296	None	None	N
R/H	0.1691	likely_benign	0.19	benign	-1.372	Destabilizing	0.997	D	0.406	neutral	N	0.486902314	None	None	N
R/I	0.5538	ambiguous	0.6965	pathogenic	0.175	Stabilizing	0.988	D	0.548	neutral	None	None	None	None	N
R/K	0.1995	likely_benign	0.25	benign	-0.619	Destabilizing	0.034	N	0.187	neutral	None	None	None	None	N
R/L	0.52	ambiguous	0.6487	pathogenic	0.175	Stabilizing	0.956	D	0.441	neutral	N	0.48862953	None	None	N
R/M	0.6077	likely_pathogenic	0.7397	pathogenic	-0.15	Destabilizing	0.999	D	0.436	neutral	None	None	None	None	N
R/N	0.7144	likely_pathogenic	0.7875	pathogenic	-0.074	Destabilizing	0.132	N	0.243	neutral	None	None	None	None	N
R/P	0.9573	likely_pathogenic	0.9755	pathogenic	-0.091	Destabilizing	0.994	D	0.477	neutral	N	0.489389999	None	None	N
R/Q	0.2106	likely_benign	0.2803	benign	-0.224	Destabilizing	0.976	D	0.445	neutral	None	None	None	None	N
R/S	0.7795	likely_pathogenic	0.8534	pathogenic	-0.832	Destabilizing	0.956	D	0.385	neutral	N	0.467309271	None	None	N
R/T	0.5431	ambiguous	0.6879	pathogenic	-0.517	Destabilizing	0.919	D	0.409	neutral	None	None	None	None	N
R/V	0.6597	likely_pathogenic	0.7718	pathogenic	-0.091	Destabilizing	0.988	D	0.549	neutral	None	None	None	None	N
R/W	0.4821	ambiguous	0.606	pathogenic	-0.192	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
R/Y	0.6948	likely_pathogenic	0.7852	pathogenic	0.109	Stabilizing	0.996	D	0.487	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.