TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17942	54049;54050;54051	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
N2AB	16301	49126;49127;49128	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
N2A	15374	46345;46346;46347	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
N2B	8877	26854;26855;26856	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
Novex-1	9002	27229;27230;27231	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
Novex-2	9069	27430;27431;27432	chr2:178605471;178605470;178605469	chr2:179470198;179470197;179470196
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-18
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6468
• Predicted PPI site: I

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/K	rs2054564830	None	0.055	N	0.317	0.138	0.232513804876	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs2054564830	None	0.055	N	0.317	0.138	0.232513804876	gnomAD-4.0.0	2.48192E-06	None	None	None	None	I	None	5.34945E-05	0	None	0	0	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
E/A	0.0807	likely_benign	0.0723	benign	-0.344	Destabilizing	None	N	0.157	neutral	N	0.411081978	None	None	I
E/C	0.6598	likely_pathogenic	0.574	pathogenic	-0.09	Destabilizing	0.676	D	0.449	neutral	None	None	None	None	I
E/D	0.0864	likely_benign	0.0887	benign	-0.306	Destabilizing	None	N	0.176	neutral	N	0.461068081	None	None	I
E/F	0.6022	likely_pathogenic	0.5323	ambiguous	-0.232	Destabilizing	0.214	N	0.487	neutral	None	None	None	None	I
E/G	0.129	likely_benign	0.0994	benign	-0.523	Destabilizing	None	N	0.204	neutral	N	0.485286161	None	None	I
E/H	0.2807	likely_benign	0.2601	benign	0.092	Stabilizing	0.356	N	0.333	neutral	None	None	None	None	I
E/I	0.2376	likely_benign	0.2065	benign	0.089	Stabilizing	0.038	N	0.555	neutral	None	None	None	None	I
E/K	0.1213	likely_benign	0.1056	benign	0.356	Stabilizing	0.055	N	0.317	neutral	N	0.455238187	None	None	I
E/L	0.2466	likely_benign	0.2083	benign	0.089	Stabilizing	None	N	0.241	neutral	None	None	None	None	I
E/M	0.3113	likely_benign	0.2754	benign	0.116	Stabilizing	0.214	N	0.479	neutral	None	None	None	None	I
E/N	0.1406	likely_benign	0.1404	benign	0.014	Stabilizing	0.038	N	0.333	neutral	None	None	None	None	I
E/P	0.4282	ambiguous	0.3668	ambiguous	-0.036	Destabilizing	0.214	N	0.446	neutral	None	None	None	None	I
E/Q	0.1126	likely_benign	0.1034	benign	0.05	Stabilizing	0.055	N	0.322	neutral	N	0.479288482	None	None	I
E/R	0.1914	likely_benign	0.1609	benign	0.569	Stabilizing	0.072	N	0.329	neutral	None	None	None	None	I
E/S	0.1153	likely_benign	0.107	benign	-0.132	Destabilizing	0.016	N	0.303	neutral	None	None	None	None	I
E/T	0.1303	likely_benign	0.1196	benign	0.019	Stabilizing	0.038	N	0.46	neutral	None	None	None	None	I
E/V	0.1625	likely_benign	0.1418	benign	-0.036	Destabilizing	0.012	N	0.482	neutral	N	0.485022376	None	None	I
E/W	0.8065	likely_pathogenic	0.7213	pathogenic	-0.089	Destabilizing	0.864	D	0.475	neutral	None	None	None	None	I
E/Y	0.453	ambiguous	0.3984	ambiguous	0.008	Stabilizing	0.356	N	0.491	neutral	None	None	None	None	I

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.