TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31468	94627;94628;94629	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
N2AB	29827	89704;89705;89706	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
N2A	28900	86923;86924;86925	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
N2B	22403	67432;67433;67434	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
Novex-1	22528	67807;67808;67809	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
Novex-2	22595	68008;68009;68010	chr2:178547123;178547122;178547121	chr2:179411850;179411849;179411848
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-117
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1704
• Predicted PPI site: I

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
Y/C	None	None	0.993	N	0.686	0.367	0.514866526686	gnomAD-4.0.0	4.10523E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	5.20291E-04	2.69843E-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
Y/A	0.6613	likely_pathogenic	0.5802	pathogenic	-2.491	Highly Destabilizing	0.707	D	0.522	neutral	None	None	None	None	I
Y/C	0.1517	likely_benign	0.14	benign	-1.325	Destabilizing	0.993	D	0.686	prob.neutral	N	0.508787457	None	None	I
Y/D	0.8154	likely_pathogenic	0.7873	pathogenic	-2.044	Highly Destabilizing	0.975	D	0.743	deleterious	D	0.525675685	None	None	I
Y/E	0.8708	likely_pathogenic	0.8592	pathogenic	-1.887	Destabilizing	0.945	D	0.633	neutral	None	None	None	None	I
Y/F	0.0613	likely_benign	0.0687	benign	-0.845	Destabilizing	0.006	N	0.237	neutral	N	0.481638141	None	None	I
Y/G	0.7298	likely_pathogenic	0.6535	pathogenic	-2.878	Highly Destabilizing	0.945	D	0.69	prob.neutral	None	None	None	None	I
Y/H	0.2664	likely_benign	0.2463	benign	-1.382	Destabilizing	0.975	D	0.543	neutral	N	0.486389302	None	None	I
Y/I	0.4815	ambiguous	0.4479	ambiguous	-1.26	Destabilizing	0.809	D	0.517	neutral	None	None	None	None	I
Y/K	0.7952	likely_pathogenic	0.7932	pathogenic	-1.656	Destabilizing	0.945	D	0.631	neutral	None	None	None	None	I
Y/L	0.4694	ambiguous	0.4401	ambiguous	-1.26	Destabilizing	0.547	D	0.437	neutral	None	None	None	None	I
Y/M	0.5663	likely_pathogenic	0.5615	ambiguous	-0.955	Destabilizing	0.985	D	0.606	neutral	None	None	None	None	I
Y/N	0.5387	ambiguous	0.4909	ambiguous	-2.259	Highly Destabilizing	0.975	D	0.687	prob.neutral	D	0.525422196	None	None	I
Y/P	0.9889	likely_pathogenic	0.9875	pathogenic	-1.674	Destabilizing	0.981	D	0.757	deleterious	None	None	None	None	I
Y/Q	0.663	likely_pathogenic	0.6326	pathogenic	-2.06	Highly Destabilizing	0.981	D	0.616	neutral	None	None	None	None	I
Y/R	0.6591	likely_pathogenic	0.6327	pathogenic	-1.37	Destabilizing	0.945	D	0.69	prob.neutral	None	None	None	None	I
Y/S	0.4737	ambiguous	0.3998	ambiguous	-2.711	Highly Destabilizing	0.928	D	0.628	neutral	N	0.513647816	None	None	I
Y/T	0.6192	likely_pathogenic	0.5497	ambiguous	-2.441	Highly Destabilizing	0.945	D	0.631	neutral	None	None	None	None	I
Y/V	0.3719	ambiguous	0.3446	ambiguous	-1.674	Destabilizing	0.547	D	0.47	neutral	None	None	None	None	I
Y/W	0.4244	ambiguous	0.458	ambiguous	-0.334	Destabilizing	0.985	D	0.547	neutral	None	None	None	None	I

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.