TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9639	29140;29141;29142	chr2:178707652;178707651;178707650	chr2:179572379;179572378;179572377
N2AB	9322	28189;28190;28191	chr2:178707652;178707651;178707650	chr2:179572379;179572378;179572377
N2A	8395	25408;25409;25410	chr2:178707652;178707651;178707650	chr2:179572379;179572378;179572377
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-82
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3495
• 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
S/G	rs2076078756	None	0.896	None	0.495	0.218	0.381580015636	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/G	rs2076078756	None	0.896	None	0.495	0.218	0.381580015636	gnomAD-4.0.0	6.56927E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46985E-05	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
S/A	0.106	likely_benign	0.0969	benign	-0.566	Destabilizing	0.132	N	0.191	neutral	None	None	None	None	N
S/C	0.2065	likely_benign	0.1801	benign	-0.363	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
S/D	0.5837	likely_pathogenic	0.4687	ambiguous	0.359	Stabilizing	0.919	D	0.473	neutral	None	None	None	None	N
S/E	0.6928	likely_pathogenic	0.5824	pathogenic	0.352	Stabilizing	0.919	D	0.491	neutral	None	None	None	None	N
S/F	0.1924	likely_benign	0.1714	benign	-0.871	Destabilizing	0.988	D	0.731	prob.delet.	None	None	None	None	N
S/G	0.1631	likely_benign	0.1547	benign	-0.785	Destabilizing	0.896	D	0.495	neutral	None	None	None	None	N
S/H	0.3361	likely_benign	0.2892	benign	-1.116	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/I	0.1873	likely_benign	0.1673	benign	-0.097	Destabilizing	0.968	D	0.69	prob.neutral	None	None	None	None	N
S/K	0.7619	likely_pathogenic	0.6612	pathogenic	-0.346	Destabilizing	0.919	D	0.496	neutral	None	None	None	None	N
S/L	0.111	likely_benign	0.1066	benign	-0.097	Destabilizing	0.851	D	0.585	neutral	None	None	None	None	N
S/M	0.2918	likely_benign	0.278	benign	-0.101	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
S/N	0.2237	likely_benign	0.2033	benign	-0.293	Destabilizing	0.896	D	0.503	neutral	None	None	None	None	N
S/P	0.8227	likely_pathogenic	0.7629	pathogenic	-0.22	Destabilizing	0.988	D	0.63	neutral	None	None	None	None	N
S/Q	0.5733	likely_pathogenic	0.5004	ambiguous	-0.367	Destabilizing	0.988	D	0.573	neutral	None	None	None	None	N
S/R	0.6126	likely_pathogenic	0.4998	ambiguous	-0.271	Destabilizing	0.984	D	0.652	neutral	None	None	None	None	N
S/T	0.0892	likely_benign	0.0873	benign	-0.346	Destabilizing	0.046	N	0.162	neutral	None	None	None	None	N
S/V	0.2012	likely_benign	0.1828	benign	-0.22	Destabilizing	0.851	D	0.614	neutral	None	None	None	None	N
S/W	0.4134	ambiguous	0.333	benign	-0.888	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
S/Y	0.194	likely_benign	0.1661	benign	-0.581	Destabilizing	0.996	D	0.728	prob.delet.	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.