TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24021	72286;72287;72288	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
N2AB	22380	67363;67364;67365	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
N2A	21453	64582;64583;64584	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
N2B	14956	45091;45092;45093	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
Novex-1	15081	45466;45467;45468	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
Novex-2	15148	45667;45668;45669	chr2:178574071;178574070;178574069	chr2:179438798;179438797;179438796
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-62
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.2895
• 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/K	rs1709204833	None	0.991	N	0.496	0.199	0.104622674875	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86008E-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	0.5663	likely_pathogenic	0.616	pathogenic	-0.26	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	N
R/C	0.2241	likely_benign	0.2688	benign	-0.097	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
R/D	0.8802	likely_pathogenic	0.8968	pathogenic	0.038	Stabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
R/E	0.5099	ambiguous	0.5653	pathogenic	0.121	Stabilizing	0.997	D	0.583	neutral	None	None	None	None	N
R/F	0.6578	likely_pathogenic	0.7134	pathogenic	-0.319	Destabilizing	0.995	D	0.849	deleterious	None	None	None	None	N
R/G	0.4481	ambiguous	0.5101	ambiguous	-0.516	Destabilizing	0.999	D	0.51	neutral	N	0.510250816	None	None	N
R/H	0.1258	likely_benign	0.1393	benign	-0.994	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	N
R/I	0.3221	likely_benign	0.3642	ambiguous	0.401	Stabilizing	0.99	D	0.587	neutral	None	None	None	None	N
R/K	0.0836	likely_benign	0.0949	benign	-0.204	Destabilizing	0.991	D	0.496	neutral	N	0.372435084	None	None	N
R/L	0.3318	likely_benign	0.3633	ambiguous	0.401	Stabilizing	0.145	N	0.416	neutral	None	None	None	None	N
R/M	0.3416	ambiguous	0.3963	ambiguous	0.116	Stabilizing	0.993	D	0.551	neutral	N	0.451093304	None	None	N
R/N	0.7571	likely_pathogenic	0.7945	pathogenic	0.317	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
R/P	0.952	likely_pathogenic	0.96	pathogenic	0.202	Stabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
R/Q	0.1169	likely_benign	0.1336	benign	0.115	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
R/S	0.6521	likely_pathogenic	0.6979	pathogenic	-0.246	Destabilizing	0.999	D	0.54	neutral	N	0.510250816	None	None	N
R/T	0.3394	likely_benign	0.3867	ambiguous	-0.008	Destabilizing	0.988	D	0.573	neutral	N	0.484565724	None	None	N
R/V	0.4191	ambiguous	0.4647	ambiguous	0.202	Stabilizing	0.965	D	0.591	neutral	None	None	None	None	N
R/W	0.2753	likely_benign	0.3242	benign	-0.177	Destabilizing	1.0	D	0.865	deleterious	N	0.474223988	None	None	N
R/Y	0.5652	likely_pathogenic	0.6275	pathogenic	0.186	Stabilizing	0.999	D	0.855	deleterious	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.