TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32144	96655;96656;96657	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
N2AB	30503	91732;91733;91734	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
N2A	29576	88951;88952;88953	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
N2B	23079	69460;69461;69462	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
Novex-1	23204	69835;69836;69837	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
Novex-2	23271	70036;70037;70038	chr2:178543543;178543542;178543541	chr2:179408270;179408269;179408268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-122
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1729
• 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
K/N	rs768078237	-2.123	0.999	N	0.817	0.382	0.259272394797	gnomAD-2.1.1	4.85E-05	None	None	None	None	N	None	1.29383E-04	0	None	0	0	None	3.27E-05	None	0	8.03E-05	0
K/N	rs768078237	-2.123	0.999	N	0.817	0.382	0.259272394797	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs768078237	-2.123	0.999	N	0.817	0.382	0.259272394797	gnomAD-4.0.0	2.85266E-05	None	None	None	None	N	None	2.66951E-05	0	None	0	0	None	0	1.64366E-04	3.56012E-05	1.09808E-05	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
K/A	0.9253	likely_pathogenic	0.9194	pathogenic	-1.467	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
K/C	0.8425	likely_pathogenic	0.8286	pathogenic	-1.415	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/D	0.9943	likely_pathogenic	0.994	pathogenic	-2.311	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
K/E	0.8699	likely_pathogenic	0.8667	pathogenic	-1.975	Destabilizing	0.99	D	0.677	prob.neutral	N	0.496727968	None	None	N
K/F	0.9662	likely_pathogenic	0.9547	pathogenic	-0.726	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/G	0.9631	likely_pathogenic	0.9522	pathogenic	-1.955	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/H	0.7459	likely_pathogenic	0.7268	pathogenic	-1.582	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/I	0.7696	likely_pathogenic	0.7834	pathogenic	-0.052	Destabilizing	0.99	D	0.853	deleterious	None	None	None	None	N
K/L	0.7476	likely_pathogenic	0.7379	pathogenic	-0.052	Destabilizing	0.979	D	0.743	deleterious	None	None	None	None	N
K/M	0.5401	ambiguous	0.5336	ambiguous	-0.458	Destabilizing	1.0	D	0.816	deleterious	N	0.51671072	None	None	N
K/N	0.9735	likely_pathogenic	0.971	pathogenic	-1.928	Destabilizing	0.999	D	0.817	deleterious	N	0.514832223	None	None	N
K/P	0.9987	likely_pathogenic	0.9985	pathogenic	-0.508	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/Q	0.452	ambiguous	0.4424	ambiguous	-1.496	Destabilizing	0.993	D	0.815	deleterious	N	0.476977872	None	None	N
K/R	0.1373	likely_benign	0.1233	benign	-0.749	Destabilizing	0.314	N	0.423	neutral	N	0.488985401	None	None	N
K/S	0.9596	likely_pathogenic	0.955	pathogenic	-2.388	Highly Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
K/T	0.813	likely_pathogenic	0.8174	pathogenic	-1.787	Destabilizing	0.999	D	0.776	deleterious	N	0.479331275	None	None	N
K/V	0.7292	likely_pathogenic	0.7341	pathogenic	-0.508	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
K/W	0.9473	likely_pathogenic	0.9273	pathogenic	-0.803	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8715	likely_pathogenic	0.8482	pathogenic	-0.46	Destabilizing	0.998	D	0.848	deleterious	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.