TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5586	16981;16982;16983	chr2:178732213;178732212;178732211	chr2:179596940;179596939;179596938
N2AB	5269	16030;16031;16032	chr2:178732213;178732212;178732211	chr2:179596940;179596939;179596938
N2A	4342	13249;13250;13251	chr2:178732213;178732212;178732211	chr2:179596940;179596939;179596938
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-39
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.3668
• 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
E/D	None	None	0.001	N	0.135	0.1	0.208816687407	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	6.07533E-05	0
E/K	rs2080668204	None	0.324	D	0.226	0.247	0.377976839388	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/Q	rs2080668204	None	0.324	D	0.298	0.212	0.306053231325	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs2080668204	None	0.324	D	0.298	0.212	0.306053231325	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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
E/A	0.0874	likely_benign	0.0962	benign	-0.473	Destabilizing	0.003	N	0.137	neutral	N	0.457292349	None	None	N
E/C	0.7703	likely_pathogenic	0.7983	pathogenic	-0.036	Destabilizing	0.981	D	0.347	neutral	None	None	None	None	N
E/D	0.0937	likely_benign	0.0965	benign	-0.436	Destabilizing	0.001	N	0.135	neutral	N	0.468490778	None	None	N
E/F	0.602	likely_pathogenic	0.6264	pathogenic	-0.344	Destabilizing	0.932	D	0.359	neutral	None	None	None	None	N
E/G	0.0965	likely_benign	0.1045	benign	-0.698	Destabilizing	0.165	N	0.303	neutral	N	0.519111599	None	None	N
E/H	0.3735	ambiguous	0.4085	ambiguous	-0.262	Destabilizing	0.932	D	0.313	neutral	None	None	None	None	N
E/I	0.2768	likely_benign	0.3083	benign	0.092	Stabilizing	0.818	D	0.381	neutral	None	None	None	None	N
E/K	0.1359	likely_benign	0.1517	benign	0.145	Stabilizing	0.324	N	0.226	neutral	D	0.525440138	None	None	N
E/L	0.2828	likely_benign	0.3115	benign	0.092	Stabilizing	0.388	N	0.364	neutral	None	None	None	None	N
E/M	0.3609	ambiguous	0.3945	ambiguous	0.297	Stabilizing	0.981	D	0.335	neutral	None	None	None	None	N
E/N	0.19	likely_benign	0.1999	benign	-0.151	Destabilizing	0.241	N	0.193	neutral	None	None	None	None	N
E/P	0.1972	likely_benign	0.2026	benign	-0.076	Destabilizing	0.002	N	0.143	neutral	None	None	None	None	N
E/Q	0.1235	likely_benign	0.137	benign	-0.099	Destabilizing	0.324	N	0.298	neutral	D	0.52274655	None	None	N
E/R	0.223	likely_benign	0.2434	benign	0.333	Stabilizing	0.818	D	0.284	neutral	None	None	None	None	N
E/S	0.1518	likely_benign	0.1601	benign	-0.331	Destabilizing	0.01	N	0.109	neutral	None	None	None	None	N
E/T	0.164	likely_benign	0.1889	benign	-0.151	Destabilizing	0.241	N	0.311	neutral	None	None	None	None	N
E/V	0.1457	likely_benign	0.1657	benign	-0.076	Destabilizing	0.324	N	0.347	neutral	N	0.517860805	None	None	N
E/W	0.7715	likely_pathogenic	0.7954	pathogenic	-0.193	Destabilizing	0.981	D	0.45	neutral	None	None	None	None	N
E/Y	0.4221	ambiguous	0.4445	ambiguous	-0.11	Destabilizing	0.932	D	0.349	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.