TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20308	61147;61148;61149	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
N2AB	18667	56224;56225;56226	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
N2A	17740	53443;53444;53445	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
N2B	11243	33952;33953;33954	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
Novex-1	11368	34327;34328;34329	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
Novex-2	11435	34528;34529;34530	chr2:178590803;178590802;178590801	chr2:179455530;179455529;179455528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-35
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1047
• 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
M/T	None	None	None	N	0.417	0.179	0.784996480802	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
M/A	0.4917	ambiguous	0.5381	ambiguous	-1.345	Destabilizing	None	N	0.412	neutral	None	None	None	None	N
M/C	0.7286	likely_pathogenic	0.7048	pathogenic	-2.823	Highly Destabilizing	0.003	N	0.572	neutral	None	None	None	None	N
M/D	0.9925	likely_pathogenic	0.9944	pathogenic	-2.17	Highly Destabilizing	None	N	0.579	neutral	None	None	None	None	N
M/E	0.9472	likely_pathogenic	0.9583	pathogenic	-1.907	Destabilizing	None	N	0.525	neutral	None	None	None	None	N
M/F	0.5503	ambiguous	0.6607	pathogenic	-0.125	Destabilizing	None	N	0.235	neutral	None	None	None	None	N
M/G	0.8489	likely_pathogenic	0.8768	pathogenic	-1.802	Destabilizing	None	N	0.537	neutral	None	None	None	None	N
M/H	0.9685	likely_pathogenic	0.9773	pathogenic	-1.83	Destabilizing	0.023	N	0.664	neutral	None	None	None	None	N
M/I	0.1086	likely_benign	0.1307	benign	-0.01	Destabilizing	None	N	0.189	neutral	N	0.287032472	None	None	N
M/K	0.923	likely_pathogenic	0.9389	pathogenic	-1.201	Destabilizing	None	N	0.47	neutral	N	0.483867583	None	None	N
M/L	0.0708	likely_benign	0.0743	benign	-0.01	Destabilizing	None	N	0.179	neutral	N	0.314896651	None	None	N
M/N	0.9509	likely_pathogenic	0.9644	pathogenic	-1.87	Destabilizing	0.004	N	0.574	neutral	None	None	None	None	N
M/P	0.972	likely_pathogenic	0.9802	pathogenic	-0.442	Destabilizing	0.001	N	0.559	neutral	None	None	None	None	N
M/Q	0.8781	likely_pathogenic	0.8955	pathogenic	-1.422	Destabilizing	0.004	N	0.329	neutral	None	None	None	None	N
M/R	0.9105	likely_pathogenic	0.929	pathogenic	-1.628	Destabilizing	0.001	N	0.513	neutral	N	0.483867583	None	None	N
M/S	0.8236	likely_pathogenic	0.8651	pathogenic	-2.133	Highly Destabilizing	None	N	0.431	neutral	None	None	None	None	N
M/T	0.4235	ambiguous	0.4759	ambiguous	-1.742	Destabilizing	None	N	0.417	neutral	N	0.483694224	None	None	N
M/V	0.0498	likely_benign	0.05	benign	-0.442	Destabilizing	None	N	0.189	neutral	N	0.259995013	None	None	N
M/W	0.9533	likely_pathogenic	0.9725	pathogenic	-0.558	Destabilizing	0.051	N	0.637	neutral	None	None	None	None	N
M/Y	0.9368	likely_pathogenic	0.9602	pathogenic	-0.453	Destabilizing	None	N	0.501	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.