TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2411	7456;7457;7458	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
N2AB	2411	7456;7457;7458	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
N2A	2411	7456;7457;7458	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
N2B	2365	7318;7319;7320	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
Novex-1	2365	7318;7319;7320	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
Novex-2	2365	7318;7319;7320	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662
Novex-3	2411	7456;7457;7458	chr2:178773937;178773936;178773935	chr2:179638664;179638663;179638662

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-13
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.2108
• 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/V	rs1333177270	-1.413	0.811	N	0.419	0.334	0.558578966169	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
M/V	rs1333177270	-1.413	0.811	N	0.419	0.334	0.558578966169	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79862E-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	0.8545	likely_pathogenic	0.8388	pathogenic	-2.562	Highly Destabilizing	0.737	D	0.405	neutral	None	None	None	None	N
M/C	0.8941	likely_pathogenic	0.8878	pathogenic	-2.216	Highly Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
M/D	0.9886	likely_pathogenic	0.9877	pathogenic	-2.166	Highly Destabilizing	0.872	D	0.536	neutral	None	None	None	None	N
M/E	0.9238	likely_pathogenic	0.9181	pathogenic	-1.969	Destabilizing	0.584	D	0.461	neutral	None	None	None	None	N
M/F	0.6805	likely_pathogenic	0.6636	pathogenic	-1.015	Destabilizing	0.993	D	0.472	neutral	None	None	None	None	N
M/G	0.9542	likely_pathogenic	0.9466	pathogenic	-3.011	Highly Destabilizing	0.85	D	0.515	neutral	None	None	None	None	N
M/H	0.8254	likely_pathogenic	0.815	pathogenic	-2.503	Highly Destabilizing	0.98	D	0.549	neutral	None	None	None	None	N
M/I	0.7623	likely_pathogenic	0.7289	pathogenic	-1.276	Destabilizing	0.969	D	0.459	neutral	N	0.448771775	None	None	N
M/K	0.4525	ambiguous	0.4227	ambiguous	-1.671	Destabilizing	0.01	N	0.291	neutral	N	0.331136024	None	None	N
M/L	0.2829	likely_benign	0.2616	benign	-1.276	Destabilizing	0.652	D	0.345	neutral	N	0.464832961	None	None	N
M/N	0.9029	likely_pathogenic	0.8973	pathogenic	-1.896	Destabilizing	0.932	D	0.548	neutral	None	None	None	None	N
M/P	0.9986	likely_pathogenic	0.9984	pathogenic	-1.687	Destabilizing	0.977	D	0.549	neutral	None	None	None	None	N
M/Q	0.5667	likely_pathogenic	0.5637	ambiguous	-1.673	Destabilizing	0.1	N	0.2	neutral	None	None	None	None	N
M/R	0.5448	ambiguous	0.5304	ambiguous	-1.569	Destabilizing	0.514	D	0.475	neutral	N	0.417120156	None	None	N
M/S	0.8352	likely_pathogenic	0.8249	pathogenic	-2.49	Highly Destabilizing	0.737	D	0.455	neutral	None	None	None	None	N
M/T	0.6156	likely_pathogenic	0.5831	pathogenic	-2.18	Highly Destabilizing	0.811	D	0.495	neutral	N	0.417459778	None	None	N
M/V	0.2454	likely_benign	0.2268	benign	-1.687	Destabilizing	0.811	D	0.419	neutral	N	0.464832961	None	None	N
M/W	0.9315	likely_pathogenic	0.9228	pathogenic	-1.291	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	N
M/Y	0.8683	likely_pathogenic	0.8574	pathogenic	-1.335	Destabilizing	0.993	D	0.547	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.