TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25059	75400;75401;75402	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
N2AB	23418	70477;70478;70479	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
N2A	22491	67696;67697;67698	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
N2B	15994	48205;48206;48207	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
Novex-1	16119	48580;48581;48582	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
Novex-2	16186	48781;48782;48783	chr2:178570957;178570956;178570955	chr2:179435684;179435683;179435682
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-70
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.6747
• 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
T/I	None	None	0.032	N	0.215	0.324	0.317084106153	gnomAD-4.0.0	2.73721E-06	None	None	None	None	I	None	5.98015E-05	0	None	0	0	None	0	0	1.79918E-06	0	0
T/K	rs1374355756	0.067	0.942	N	0.337	0.412	0.433823933641	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/K	rs1374355756	0.067	0.942	N	0.337	0.412	0.433823933641	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/K	rs1374355756	0.067	0.942	N	0.337	0.412	0.433823933641	gnomAD-4.0.0	5.57834E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.62964E-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
T/A	0.1885	likely_benign	0.162	benign	-0.248	Destabilizing	0.025	N	0.113	neutral	N	0.470575786	None	None	I
T/C	0.7714	likely_pathogenic	0.7555	pathogenic	-0.349	Destabilizing	0.998	D	0.422	neutral	None	None	None	None	I
T/D	0.8699	likely_pathogenic	0.8464	pathogenic	0.409	Stabilizing	0.978	D	0.345	neutral	None	None	None	None	I
T/E	0.8223	likely_pathogenic	0.8009	pathogenic	0.338	Stabilizing	0.978	D	0.333	neutral	None	None	None	None	I
T/F	0.7963	likely_pathogenic	0.7616	pathogenic	-0.849	Destabilizing	0.956	D	0.523	neutral	None	None	None	None	I
T/G	0.4753	ambiguous	0.4377	ambiguous	-0.345	Destabilizing	0.754	D	0.448	neutral	None	None	None	None	I
T/H	0.6891	likely_pathogenic	0.6537	pathogenic	-0.527	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
T/I	0.6536	likely_pathogenic	0.6342	pathogenic	-0.117	Destabilizing	0.032	N	0.215	neutral	N	0.470611997	None	None	I
T/K	0.6869	likely_pathogenic	0.6564	pathogenic	-0.177	Destabilizing	0.942	D	0.337	neutral	N	0.506611157	None	None	I
T/L	0.3402	ambiguous	0.3072	benign	-0.117	Destabilizing	0.303	N	0.4	neutral	None	None	None	None	I
T/M	0.2492	likely_benign	0.2333	benign	-0.178	Destabilizing	0.988	D	0.399	neutral	None	None	None	None	I
T/N	0.3727	ambiguous	0.3202	benign	-0.068	Destabilizing	0.993	D	0.328	neutral	None	None	None	None	I
T/P	0.6998	likely_pathogenic	0.6362	pathogenic	-0.134	Destabilizing	0.97	D	0.386	neutral	N	0.479779483	None	None	I
T/Q	0.5545	ambiguous	0.5272	ambiguous	-0.212	Destabilizing	0.993	D	0.369	neutral	None	None	None	None	I
T/R	0.5812	likely_pathogenic	0.5545	ambiguous	0.045	Stabilizing	0.97	D	0.384	neutral	N	0.518462946	None	None	I
T/S	0.1968	likely_benign	0.1785	benign	-0.274	Destabilizing	0.698	D	0.357	neutral	N	0.490774912	None	None	I
T/V	0.4569	ambiguous	0.444	ambiguous	-0.134	Destabilizing	0.303	N	0.361	neutral	None	None	None	None	I
T/W	0.9449	likely_pathogenic	0.9328	pathogenic	-0.915	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	I
T/Y	0.8096	likely_pathogenic	0.7712	pathogenic	-0.587	Destabilizing	0.978	D	0.533	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.