TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28123	84592;84593;84594	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
N2AB	26482	79669;79670;79671	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
N2A	25555	76888;76889;76890	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
N2B	19058	57397;57398;57399	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
Novex-1	19183	57772;57773;57774	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
Novex-2	19250	57973;57974;57975	chr2:178561765;178561764;178561763	chr2:179426492;179426491;179426490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-92
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1994
• 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
S/N	rs1703752029	None	0.007	N	0.132	0.079	0.148003135375	gnomAD-4.0.0	6.84307E-07	None	None	None	None	N	None	2.98846E-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
S/A	0.0739	likely_benign	0.0743	benign	-0.912	Destabilizing	0.543	D	0.303	neutral	None	None	None	None	N
S/C	0.0765	likely_benign	0.0775	benign	-0.614	Destabilizing	0.994	D	0.411	neutral	N	0.461358869	None	None	N
S/D	0.476	ambiguous	0.4274	ambiguous	-0.3	Destabilizing	0.59	D	0.32	neutral	None	None	None	None	N
S/E	0.4968	ambiguous	0.4448	ambiguous	-0.284	Destabilizing	0.742	D	0.307	neutral	None	None	None	None	N
S/F	0.1728	likely_benign	0.1745	benign	-1.084	Destabilizing	0.953	D	0.467	neutral	None	None	None	None	N
S/G	0.1042	likely_benign	0.1062	benign	-1.173	Destabilizing	0.309	N	0.309	neutral	N	0.468188841	None	None	N
S/H	0.321	likely_benign	0.2955	benign	-1.582	Destabilizing	0.953	D	0.427	neutral	None	None	None	None	N
S/I	0.1372	likely_benign	0.1418	benign	-0.317	Destabilizing	0.028	N	0.275	neutral	N	0.520444458	None	None	N
S/K	0.566	likely_pathogenic	0.4802	ambiguous	-0.673	Destabilizing	0.037	N	0.124	neutral	None	None	None	None	N
S/L	0.0787	likely_benign	0.0833	benign	-0.317	Destabilizing	0.373	N	0.361	neutral	None	None	None	None	N
S/M	0.1413	likely_benign	0.1457	benign	-0.036	Destabilizing	0.953	D	0.428	neutral	None	None	None	None	N
S/N	0.136	likely_benign	0.1259	benign	-0.708	Destabilizing	0.007	N	0.132	neutral	N	0.440463522	None	None	N
S/P	0.901	likely_pathogenic	0.8899	pathogenic	-0.482	Destabilizing	0.984	D	0.453	neutral	None	None	None	None	N
S/Q	0.432	ambiguous	0.3878	ambiguous	-0.842	Destabilizing	0.91	D	0.413	neutral	None	None	None	None	N
S/R	0.4932	ambiguous	0.4165	ambiguous	-0.582	Destabilizing	0.521	D	0.459	neutral	N	0.44088481	None	None	N
S/T	0.0754	likely_benign	0.077	benign	-0.733	Destabilizing	0.012	N	0.056	neutral	N	0.373923525	None	None	N
S/V	0.1347	likely_benign	0.139	benign	-0.482	Destabilizing	0.373	N	0.354	neutral	None	None	None	None	N
S/W	0.3286	likely_benign	0.3444	ambiguous	-1.03	Destabilizing	0.996	D	0.524	neutral	None	None	None	None	N
S/Y	0.1638	likely_benign	0.1645	benign	-0.765	Destabilizing	0.984	D	0.474	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.