TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30696	92311;92312;92313	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
N2AB	29055	87388;87389;87390	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
N2A	28128	84607;84608;84609	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
N2B	21631	65116;65117;65118	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
Novex-1	21756	65491;65492;65493	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
Novex-2	21823	65692;65693;65694	chr2:178549636;178549635;178549634	chr2:179414363;179414362;179414361
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-111
• Domain position: 78
• Structural Position: 110
• Q(SASA): 0.1032
• 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
A/V	None	None	1.0	D	0.715	0.687	0.663846892577	gnomAD-4.0.0	2.05268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99494E-07	2.31906E-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
A/C	0.8156	likely_pathogenic	0.8153	pathogenic	-1.866	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/D	0.9951	likely_pathogenic	0.9954	pathogenic	-3.054	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/E	0.993	likely_pathogenic	0.9936	pathogenic	-2.818	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.571155311	None	None	N
A/F	0.9831	likely_pathogenic	0.9863	pathogenic	-0.769	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/G	0.2518	likely_benign	0.2302	benign	-2.099	Highly Destabilizing	1.0	D	0.638	neutral	N	0.504472282	None	None	N
A/H	0.9957	likely_pathogenic	0.9956	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/I	0.9365	likely_pathogenic	0.9595	pathogenic	-0.349	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/K	0.9982	likely_pathogenic	0.9983	pathogenic	-1.481	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/L	0.897	likely_pathogenic	0.9124	pathogenic	-0.349	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/M	0.9307	likely_pathogenic	0.9466	pathogenic	-0.917	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/N	0.9852	likely_pathogenic	0.9852	pathogenic	-1.986	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/P	0.6513	likely_pathogenic	0.634	pathogenic	-0.742	Destabilizing	1.0	D	0.851	deleterious	D	0.537339884	None	None	N
A/Q	0.9883	likely_pathogenic	0.988	pathogenic	-1.716	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
A/R	0.9938	likely_pathogenic	0.9934	pathogenic	-1.575	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
A/S	0.2984	likely_benign	0.3179	benign	-2.341	Highly Destabilizing	1.0	D	0.625	neutral	N	0.521536126	None	None	N
A/T	0.6461	likely_pathogenic	0.711	pathogenic	-1.988	Destabilizing	1.0	D	0.798	deleterious	D	0.549413297	None	None	N
A/V	0.7345	likely_pathogenic	0.8013	pathogenic	-0.742	Destabilizing	1.0	D	0.715	prob.delet.	D	0.557771089	None	None	N
A/W	0.9986	likely_pathogenic	0.9988	pathogenic	-1.488	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/Y	0.9943	likely_pathogenic	0.9947	pathogenic	-1.104	Destabilizing	1.0	D	0.879	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.