TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24294	73105;73106;73107	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
N2AB	22653	68182;68183;68184	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
N2A	21726	65401;65402;65403	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
N2B	15229	45910;45911;45912	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
Novex-1	15354	46285;46286;46287	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
Novex-2	15421	46486;46487;46488	chr2:178573252;178573251;178573250	chr2:179437979;179437978;179437977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-64
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1357
• 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
E/A	rs766386367	-2.119	0.999	N	0.653	0.547	0.523910806359	gnomAD-2.1.1	2.06E-05	None	None	None	None	N	None	0	1.48518E-04	None	0	0	None	0	None	0	0	0
E/A	rs766386367	-2.119	0.999	N	0.653	0.547	0.523910806359	gnomAD-4.0.0	8.05065E-06	None	None	None	None	N	None	0	1.16009E-04	None	0	0	None	0	0	0	0	0
E/K	rs1708891748	None	0.999	N	0.585	0.38	0.383590876969	gnomAD-4.0.0	6.87736E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0292E-07	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	0.4431	ambiguous	0.3867	ambiguous	-0.513	Destabilizing	0.999	D	0.653	neutral	N	0.499249637	None	None	N
E/C	0.9269	likely_pathogenic	0.9175	pathogenic	0.274	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/D	0.8186	likely_pathogenic	0.7859	pathogenic	-1.359	Destabilizing	0.999	D	0.495	neutral	N	0.515810182	None	None	N
E/F	0.9679	likely_pathogenic	0.9652	pathogenic	-0.236	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.7276	likely_pathogenic	0.6231	pathogenic	-0.93	Destabilizing	1.0	D	0.747	deleterious	N	0.519684523	None	None	N
E/H	0.8864	likely_pathogenic	0.8799	pathogenic	-0.14	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/I	0.7924	likely_pathogenic	0.8078	pathogenic	0.671	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/K	0.7806	likely_pathogenic	0.7211	pathogenic	-0.324	Destabilizing	0.999	D	0.585	neutral	N	0.47691542	None	None	N
E/L	0.8862	likely_pathogenic	0.8981	pathogenic	0.671	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.7585	likely_pathogenic	0.748	pathogenic	1.247	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/N	0.8689	likely_pathogenic	0.8478	pathogenic	-0.74	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.9984	likely_pathogenic	0.9974	pathogenic	0.293	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Q	0.2422	likely_benign	0.2117	benign	-0.384	Destabilizing	1.0	D	0.649	neutral	N	0.486870603	None	None	N
E/R	0.8478	likely_pathogenic	0.8046	pathogenic	-0.43	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.5759	likely_pathogenic	0.5038	ambiguous	-1.271	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
E/T	0.7444	likely_pathogenic	0.7073	pathogenic	-0.859	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/V	0.647	likely_pathogenic	0.6589	pathogenic	0.293	Stabilizing	1.0	D	0.755	deleterious	N	0.488196046	None	None	N
E/W	0.9947	likely_pathogenic	0.9938	pathogenic	-0.425	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/Y	0.957	likely_pathogenic	0.9509	pathogenic	-0.005	Destabilizing	1.0	D	0.767	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.