TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30204	90835;90836;90837	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
N2AB	28563	85912;85913;85914	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
N2A	27636	83131;83132;83133	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
N2B	21139	63640;63641;63642	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
Novex-1	21264	64015;64016;64017	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
Novex-2	21331	64216;64217;64218	chr2:178552290;178552289;178552288	chr2:179417017;179417016;179417015
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-148
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0825
• 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
V/A	rs1699759872	None	0.052	N	0.585	0.239	0.469415673434	gnomAD-4.0.0	6.84399E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99588E-07	0	0
V/I	rs898701169	None	None	N	0.274	0.052	0.0954503805726	gnomAD-4.0.0	6.84415E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16139E-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
V/A	0.5883	likely_pathogenic	0.4889	ambiguous	-1.746	Destabilizing	0.052	N	0.585	neutral	N	0.510485676	None	None	N
V/C	0.8687	likely_pathogenic	0.8117	pathogenic	-1.16	Destabilizing	0.935	D	0.776	deleterious	None	None	None	None	N
V/D	0.9944	likely_pathogenic	0.9902	pathogenic	-2.839	Highly Destabilizing	0.484	N	0.846	deleterious	N	0.480534773	None	None	N
V/E	0.9859	likely_pathogenic	0.9735	pathogenic	-2.523	Highly Destabilizing	0.555	D	0.817	deleterious	None	None	None	None	N
V/F	0.4295	ambiguous	0.36	ambiguous	-0.99	Destabilizing	0.117	N	0.767	deleterious	N	0.467657531	None	None	N
V/G	0.8466	likely_pathogenic	0.7581	pathogenic	-2.358	Highly Destabilizing	0.484	N	0.831	deleterious	N	0.480281284	None	None	N
V/H	0.9918	likely_pathogenic	0.9845	pathogenic	-2.527	Highly Destabilizing	0.935	D	0.847	deleterious	None	None	None	None	N
V/I	0.0682	likely_benign	0.0691	benign	0.015	Stabilizing	None	N	0.274	neutral	N	0.447319632	None	None	N
V/K	0.988	likely_pathogenic	0.9761	pathogenic	-1.382	Destabilizing	0.555	D	0.823	deleterious	None	None	None	None	N
V/L	0.1307	likely_benign	0.1047	benign	0.015	Stabilizing	None	N	0.303	neutral	N	0.446972915	None	None	N
V/M	0.2251	likely_benign	0.1891	benign	-0.197	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	N
V/N	0.9733	likely_pathogenic	0.9556	pathogenic	-2.066	Highly Destabilizing	0.791	D	0.851	deleterious	None	None	None	None	N
V/P	0.9722	likely_pathogenic	0.9572	pathogenic	-0.549	Destabilizing	0.791	D	0.843	deleterious	None	None	None	None	N
V/Q	0.9795	likely_pathogenic	0.9603	pathogenic	-1.682	Destabilizing	0.791	D	0.843	deleterious	None	None	None	None	N
V/R	0.9796	likely_pathogenic	0.9596	pathogenic	-1.63	Destabilizing	0.555	D	0.849	deleterious	None	None	None	None	N
V/S	0.9157	likely_pathogenic	0.8671	pathogenic	-2.543	Highly Destabilizing	0.262	N	0.809	deleterious	None	None	None	None	N
V/T	0.8129	likely_pathogenic	0.7354	pathogenic	-2.062	Highly Destabilizing	0.149	N	0.645	neutral	None	None	None	None	N
V/W	0.9853	likely_pathogenic	0.9723	pathogenic	-1.675	Destabilizing	0.935	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9468	likely_pathogenic	0.9054	pathogenic	-1.206	Destabilizing	0.555	D	0.77	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.