TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28120	84583;84584;84585	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
N2AB	26479	79660;79661;79662	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
N2A	25552	76879;76880;76881	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
N2B	19055	57388;57389;57390	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
Novex-1	19180	57763;57764;57765	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
Novex-2	19247	57964;57965;57966	chr2:178561774;178561773;178561772	chr2:179426501;179426500;179426499
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: Fn3-92
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.3714
• 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
T/I	None	None	None	N	0.109	0.112	0.0762999501168	gnomAD-4.0.0	1.36861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-06	0	0
T/K	rs1261670625	-0.448	0.055	N	0.421	0.111	0.0762999501168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/K	rs1261670625	-0.448	0.055	N	0.421	0.111	0.0762999501168	gnomAD-4.0.0	2.60035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.41813E-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
T/A	0.0814	likely_benign	0.0823	benign	-0.742	Destabilizing	None	N	0.071	neutral	N	0.52128982	None	None	N
T/C	0.3528	ambiguous	0.4047	ambiguous	-0.388	Destabilizing	0.356	N	0.419	neutral	None	None	None	None	N
T/D	0.3968	ambiguous	0.4001	ambiguous	0.416	Stabilizing	0.072	N	0.432	neutral	None	None	None	None	N
T/E	0.2777	likely_benign	0.2692	benign	0.358	Stabilizing	0.072	N	0.38	neutral	None	None	None	None	N
T/F	0.2375	likely_benign	0.2517	benign	-1.212	Destabilizing	0.214	N	0.467	neutral	None	None	None	None	N
T/G	0.2323	likely_benign	0.2596	benign	-0.886	Destabilizing	0.072	N	0.387	neutral	None	None	None	None	N
T/H	0.2164	likely_benign	0.2091	benign	-1.153	Destabilizing	0.864	D	0.429	neutral	None	None	None	None	N
T/I	0.104	likely_benign	0.1108	benign	-0.473	Destabilizing	None	N	0.109	neutral	N	0.43605778	None	None	N
T/K	0.1615	likely_benign	0.1386	benign	-0.345	Destabilizing	0.055	N	0.421	neutral	N	0.41594908	None	None	N
T/L	0.0841	likely_benign	0.0879	benign	-0.473	Destabilizing	0.002	N	0.329	neutral	None	None	None	None	N
T/M	0.0851	likely_benign	0.0903	benign	-0.189	Destabilizing	0.214	N	0.429	neutral	None	None	None	None	N
T/N	0.1043	likely_benign	0.1024	benign	-0.168	Destabilizing	0.072	N	0.378	neutral	None	None	None	None	N
T/P	0.2424	likely_benign	0.2232	benign	-0.534	Destabilizing	0.295	N	0.453	neutral	N	0.489107872	None	None	N
T/Q	0.1768	likely_benign	0.171	benign	-0.38	Destabilizing	0.356	N	0.44	neutral	None	None	None	None	N
T/R	0.1576	likely_benign	0.1371	benign	-0.104	Destabilizing	0.295	N	0.453	neutral	N	0.504202783	None	None	N
T/S	0.1082	likely_benign	0.1147	benign	-0.484	Destabilizing	0.002	N	0.13	neutral	N	0.47442138	None	None	N
T/V	0.0896	likely_benign	0.0996	benign	-0.534	Destabilizing	None	N	0.064	neutral	None	None	None	None	N
T/W	0.6159	likely_pathogenic	0.6333	pathogenic	-1.135	Destabilizing	0.864	D	0.471	neutral	None	None	None	None	N
T/Y	0.2896	likely_benign	0.292	benign	-0.877	Destabilizing	0.356	N	0.459	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.