TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19601	59026;59027;59028	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
N2AB	17960	54103;54104;54105	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
N2A	17033	51322;51323;51324	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
N2B	10536	31831;31832;31833	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
Novex-1	10661	32206;32207;32208	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
Novex-2	10728	32407;32408;32409	chr2:178593407;178593406;178593405	chr2:179458134;179458133;179458132
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-30
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4494
• 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
N/S	None	None	0.201	N	0.394	0.162	0.16115917748	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43303E-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
N/A	0.1818	likely_benign	0.2172	benign	-0.541	Destabilizing	0.25	N	0.433	neutral	None	None	None	None	N
N/C	0.2447	likely_benign	0.2666	benign	0.225	Stabilizing	0.992	D	0.57	neutral	None	None	None	None	N
N/D	0.187	likely_benign	0.2074	benign	-0.153	Destabilizing	0.201	N	0.399	neutral	N	0.471687719	None	None	N
N/E	0.2404	likely_benign	0.2901	benign	-0.117	Destabilizing	0.009	N	0.191	neutral	None	None	None	None	N
N/F	0.4533	ambiguous	0.4914	ambiguous	-0.531	Destabilizing	0.85	D	0.584	neutral	None	None	None	None	N
N/G	0.2285	likely_benign	0.2581	benign	-0.819	Destabilizing	0.4	N	0.371	neutral	None	None	None	None	N
N/H	0.103	likely_benign	0.1097	benign	-0.78	Destabilizing	0.896	D	0.468	neutral	N	0.489409475	None	None	N
N/I	0.1831	likely_benign	0.2076	benign	0.132	Stabilizing	0.379	N	0.583	neutral	N	0.49570073	None	None	N
N/K	0.1724	likely_benign	0.2052	benign	-0.228	Destabilizing	0.004	N	0.169	neutral	N	0.415159646	None	None	N
N/L	0.1987	likely_benign	0.2266	benign	0.132	Stabilizing	0.005	N	0.464	neutral	None	None	None	None	N
N/M	0.2471	likely_benign	0.2788	benign	0.425	Stabilizing	0.85	D	0.569	neutral	None	None	None	None	N
N/P	0.6019	likely_pathogenic	0.6451	pathogenic	-0.063	Destabilizing	0.92	D	0.617	neutral	None	None	None	None	N
N/Q	0.1902	likely_benign	0.2277	benign	-0.606	Destabilizing	0.447	N	0.415	neutral	None	None	None	None	N
N/R	0.2077	likely_benign	0.2424	benign	-0.291	Destabilizing	0.447	N	0.356	neutral	None	None	None	None	N
N/S	0.0968	likely_benign	0.1064	benign	-0.522	Destabilizing	0.201	N	0.394	neutral	N	0.425509926	None	None	N
N/T	0.1183	likely_benign	0.1368	benign	-0.316	Destabilizing	0.549	D	0.371	neutral	N	0.430609101	None	None	N
N/V	0.1841	likely_benign	0.2148	benign	-0.063	Destabilizing	0.447	N	0.489	neutral	None	None	None	None	N
N/W	0.6638	likely_pathogenic	0.6979	pathogenic	-0.425	Destabilizing	0.992	D	0.618	neutral	None	None	None	None	N
N/Y	0.1586	likely_benign	0.1633	benign	-0.207	Destabilizing	0.963	D	0.587	neutral	N	0.513286413	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.