TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30876	92851;92852;92853	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
N2AB	29235	87928;87929;87930	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
N2A	28308	85147;85148;85149	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
N2B	21811	65656;65657;65658	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
Novex-1	21936	66031;66032;66033	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
Novex-2	22003	66232;66233;66234	chr2:178549000;178548999;178548998	chr2:179413727;179413726;179413725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-113
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1875
• 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
C/Y	None	None	0.681	N	0.528	0.219	0.632893766264	gnomAD-4.0.0	6.84171E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99426E-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
C/A	0.3366	likely_benign	0.2997	benign	-1.826	Destabilizing	0.25	N	0.363	neutral	None	None	None	None	N
C/D	0.7927	likely_pathogenic	0.6998	pathogenic	-0.829	Destabilizing	0.85	D	0.551	neutral	None	None	None	None	N
C/E	0.8439	likely_pathogenic	0.7661	pathogenic	-0.639	Destabilizing	0.92	D	0.547	neutral	None	None	None	None	N
C/F	0.2371	likely_benign	0.2003	benign	-1.1	Destabilizing	0.681	D	0.523	neutral	N	0.476786895	None	None	N
C/G	0.2572	likely_benign	0.2142	benign	-2.19	Highly Destabilizing	0.004	N	0.429	neutral	N	0.390802706	None	None	N
C/H	0.6289	likely_pathogenic	0.526	ambiguous	-2.227	Highly Destabilizing	0.992	D	0.55	neutral	None	None	None	None	N
C/I	0.3436	ambiguous	0.3087	benign	-0.853	Destabilizing	0.447	N	0.445	neutral	None	None	None	None	N
C/K	0.8615	likely_pathogenic	0.7797	pathogenic	-1.072	Destabilizing	0.85	D	0.551	neutral	None	None	None	None	N
C/L	0.3891	ambiguous	0.3263	benign	-0.853	Destabilizing	0.25	N	0.417	neutral	None	None	None	None	N
C/M	0.5486	ambiguous	0.4961	ambiguous	0.286	Stabilizing	0.92	D	0.531	neutral	None	None	None	None	N
C/N	0.5549	ambiguous	0.4664	ambiguous	-1.444	Destabilizing	0.85	D	0.559	neutral	None	None	None	None	N
C/P	0.8903	likely_pathogenic	0.843	pathogenic	-1.153	Destabilizing	0.972	D	0.561	neutral	None	None	None	None	N
C/Q	0.7169	likely_pathogenic	0.6145	pathogenic	-1.106	Destabilizing	0.972	D	0.581	neutral	None	None	None	None	N
C/R	0.5803	likely_pathogenic	0.4653	ambiguous	-1.238	Destabilizing	0.896	D	0.561	neutral	N	0.478613692	None	None	N
C/S	0.28	likely_benign	0.2422	benign	-1.905	Destabilizing	0.549	D	0.44	neutral	N	0.442594176	None	None	N
C/T	0.3627	ambiguous	0.319	benign	-1.513	Destabilizing	0.617	D	0.438	neutral	None	None	None	None	N
C/V	0.2555	likely_benign	0.2351	benign	-1.153	Destabilizing	0.002	N	0.243	neutral	None	None	None	None	N
C/W	0.626	likely_pathogenic	0.5245	ambiguous	-1.267	Destabilizing	0.009	N	0.366	neutral	N	0.473646509	None	None	N
C/Y	0.3896	ambiguous	0.3074	benign	-1.187	Destabilizing	0.681	D	0.528	neutral	N	0.463780312	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.