TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28346	85261;85262;85263	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
N2AB	26705	80338;80339;80340	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
N2A	25778	77557;77558;77559	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
N2B	19281	58066;58067;58068	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
Novex-1	19406	58441;58442;58443	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
Novex-2	19473	58642;58643;58644	chr2:178561096;178561095;178561094	chr2:179425823;179425822;179425821
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-94
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.1525
• 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
I/L	rs912296403	None	0.162	N	0.376	0.045	0.336892272479	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/L	rs912296403	None	0.162	N	0.376	0.045	0.336892272479	gnomAD-4.0.0	2.02992E-06	None	None	None	None	N	None	1.74727E-05	0	None	0	0	None	0	0	1.20492E-06	0	0
I/N	None	None	0.979	N	0.833	0.463	0.783919937588	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
I/A	0.7844	likely_pathogenic	0.7891	pathogenic	-2.076	Highly Destabilizing	0.37	N	0.585	neutral	None	None	None	None	N
I/C	0.86	likely_pathogenic	0.8652	pathogenic	-1.208	Destabilizing	0.996	D	0.729	deleterious	None	None	None	None	N
I/D	0.9891	likely_pathogenic	0.9881	pathogenic	-2.483	Highly Destabilizing	0.984	D	0.837	deleterious	None	None	None	None	N
I/E	0.9528	likely_pathogenic	0.9554	pathogenic	-2.216	Highly Destabilizing	0.953	D	0.806	deleterious	None	None	None	None	N
I/F	0.5047	ambiguous	0.4831	ambiguous	-1.229	Destabilizing	0.883	D	0.707	prob.delet.	N	0.474189487	None	None	N
I/G	0.9621	likely_pathogenic	0.9602	pathogenic	-2.627	Highly Destabilizing	0.953	D	0.772	deleterious	None	None	None	None	N
I/H	0.9333	likely_pathogenic	0.9363	pathogenic	-2.133	Highly Destabilizing	0.996	D	0.826	deleterious	None	None	None	None	N
I/K	0.8847	likely_pathogenic	0.8929	pathogenic	-1.58	Destabilizing	0.953	D	0.804	deleterious	None	None	None	None	N
I/L	0.2095	likely_benign	0.2208	benign	-0.472	Destabilizing	0.162	N	0.376	neutral	N	0.520092168	None	None	N
I/M	0.2294	likely_benign	0.2282	benign	-0.383	Destabilizing	0.938	D	0.739	deleterious	N	0.490990296	None	None	N
I/N	0.8826	likely_pathogenic	0.8866	pathogenic	-2.115	Highly Destabilizing	0.979	D	0.833	deleterious	N	0.50934804	None	None	N
I/P	0.9945	likely_pathogenic	0.9946	pathogenic	-0.99	Destabilizing	0.984	D	0.838	deleterious	None	None	None	None	N
I/Q	0.8997	likely_pathogenic	0.9049	pathogenic	-1.872	Destabilizing	0.984	D	0.825	deleterious	None	None	None	None	N
I/R	0.8349	likely_pathogenic	0.85	pathogenic	-1.515	Destabilizing	0.953	D	0.827	deleterious	None	None	None	None	N
I/S	0.8569	likely_pathogenic	0.8703	pathogenic	-2.741	Highly Destabilizing	0.938	D	0.747	deleterious	N	0.506306166	None	None	N
I/T	0.6715	likely_pathogenic	0.6852	pathogenic	-2.314	Highly Destabilizing	0.682	D	0.681	prob.neutral	N	0.507066634	None	None	N
I/V	0.066	likely_benign	0.0627	benign	-0.99	Destabilizing	0.001	N	0.145	neutral	N	0.409345608	None	None	N
I/W	0.9786	likely_pathogenic	0.9751	pathogenic	-1.637	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
I/Y	0.8813	likely_pathogenic	0.8912	pathogenic	-1.262	Destabilizing	0.953	D	0.786	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.