TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33206	99841;99842;99843	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
N2AB	31565	94918;94919;94920	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
N2A	30638	92137;92138;92139	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
N2B	24141	72646;72647;72648	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
Novex-1	24266	73021;73022;73023	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
Novex-2	24333	73222;73223;73224	chr2:178537591;178537590;178537589	chr2:179402318;179402317;179402316
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-157
• Domain position: 4
• Structural Position: 13
• Q(SASA): 0.2501
• 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
Y/D	None	None	1.0	N	0.76	0.543	0.584023569625	gnomAD-4.0.0	3.18333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71785E-06	0	0
Y/H	None	None	1.0	N	0.653	0.459	0.321393169273	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
Y/A	0.8498	likely_pathogenic	0.874	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
Y/C	0.4489	ambiguous	0.5906	pathogenic	-1.187	Destabilizing	1.0	D	0.733	prob.delet.	N	0.501095402	None	None	N
Y/D	0.8826	likely_pathogenic	0.8969	pathogenic	-1.11	Destabilizing	1.0	D	0.76	deleterious	N	0.501095402	None	None	N
Y/E	0.9454	likely_pathogenic	0.9527	pathogenic	-0.98	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
Y/F	0.1651	likely_benign	0.2016	benign	-0.729	Destabilizing	0.996	D	0.56	neutral	N	0.471119211	None	None	N
Y/G	0.8427	likely_pathogenic	0.8659	pathogenic	-2.472	Highly Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
Y/H	0.6165	likely_pathogenic	0.6564	pathogenic	-0.865	Destabilizing	1.0	D	0.653	neutral	N	0.500922043	None	None	N
Y/I	0.5757	likely_pathogenic	0.65	pathogenic	-1.096	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
Y/K	0.9307	likely_pathogenic	0.9336	pathogenic	-1.476	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
Y/L	0.6284	likely_pathogenic	0.7084	pathogenic	-1.096	Destabilizing	0.991	D	0.676	prob.neutral	None	None	None	None	N
Y/M	0.7951	likely_pathogenic	0.841	pathogenic	-0.935	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
Y/N	0.6185	likely_pathogenic	0.6523	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.737	prob.delet.	N	0.501095402	None	None	N
Y/P	0.981	likely_pathogenic	0.9795	pathogenic	-1.441	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Y/Q	0.8864	likely_pathogenic	0.9045	pathogenic	-1.819	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
Y/R	0.8628	likely_pathogenic	0.8768	pathogenic	-1.208	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
Y/S	0.6941	likely_pathogenic	0.7346	pathogenic	-2.503	Highly Destabilizing	1.0	D	0.731	prob.delet.	N	0.500748685	None	None	N
Y/T	0.7896	likely_pathogenic	0.8166	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
Y/V	0.5211	ambiguous	0.589	pathogenic	-1.441	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
Y/W	0.7239	likely_pathogenic	0.7468	pathogenic	-0.282	Destabilizing	1.0	D	0.653	neutral	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.