TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20431	61516;61517;61518	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
N2AB	18790	56593;56594;56595	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
N2A	17863	53812;53813;53814	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
N2B	11366	34321;34322;34323	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
Novex-1	11491	34696;34697;34698	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
Novex-2	11558	34897;34898;34899	chr2:178590434;178590433;178590432	chr2:179455161;179455160;179455159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-36
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.2273
• 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	rs2049959864	None	1.0	N	0.585	0.406	0.606927088724	gnomAD-4.0.0	1.59432E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43815E-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	0.4185	ambiguous	0.4247	ambiguous	-0.517	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/D	0.7448	likely_pathogenic	0.7551	pathogenic	-1.454	Destabilizing	1.0	D	0.767	deleterious	N	0.511496901	None	None	N
A/E	0.5779	likely_pathogenic	0.5899	pathogenic	-1.333	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
A/F	0.5215	ambiguous	0.4866	ambiguous	-0.596	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/G	0.2737	likely_benign	0.2542	benign	-1.056	Destabilizing	1.0	D	0.503	neutral	N	0.506301725	None	None	N
A/H	0.6356	likely_pathogenic	0.6223	pathogenic	-1.347	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/I	0.3855	ambiguous	0.3618	ambiguous	0.277	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/K	0.7835	likely_pathogenic	0.7952	pathogenic	-0.931	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/L	0.3401	ambiguous	0.3155	benign	0.277	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
A/M	0.3706	ambiguous	0.3536	ambiguous	0.169	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/N	0.4348	ambiguous	0.4178	ambiguous	-1.009	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/P	0.9188	likely_pathogenic	0.9064	pathogenic	0.003	Stabilizing	1.0	D	0.761	deleterious	N	0.502434701	None	None	N
A/Q	0.4947	ambiguous	0.486	ambiguous	-0.942	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/R	0.671	likely_pathogenic	0.6853	pathogenic	-0.875	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/S	0.1222	likely_benign	0.1195	benign	-1.372	Destabilizing	1.0	D	0.512	neutral	N	0.407500168	None	None	N
A/T	0.1528	likely_benign	0.1463	benign	-1.131	Destabilizing	1.0	D	0.661	neutral	N	0.432859972	None	None	N
A/V	0.2249	likely_benign	0.2144	benign	0.003	Stabilizing	1.0	D	0.585	neutral	N	0.495258012	None	None	N
A/W	0.8958	likely_pathogenic	0.8821	pathogenic	-1.231	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
A/Y	0.6249	likely_pathogenic	0.6044	pathogenic	-0.625	Destabilizing	1.0	D	0.802	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.