TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29197	87814;87815;87816	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
N2AB	27556	82891;82892;82893	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
N2A	26629	80110;80111;80112	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
N2B	20132	60619;60620;60621	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
Novex-1	20257	60994;60995;60996	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
Novex-2	20324	61195;61196;61197	chr2:178557765;178557764;178557763	chr2:179422492;179422491;179422490
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: Fn3-100
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.0989
• 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/R	None	None	0.106	N	0.529	0.317	0.626322489162	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85783E-06	0	0
M/T	None	None	None	N	0.327	0.324	0.60311569301	gnomAD-4.0.0	1.59104E-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
M/A	0.6039	likely_pathogenic	0.6222	pathogenic	-1.825	Destabilizing	0.007	N	0.417	neutral	None	None	None	None	N
M/C	0.6153	likely_pathogenic	0.6608	pathogenic	-1.578	Destabilizing	0.628	D	0.535	neutral	None	None	None	None	N
M/D	0.9792	likely_pathogenic	0.9789	pathogenic	-0.641	Destabilizing	0.072	N	0.555	neutral	None	None	None	None	N
M/E	0.8898	likely_pathogenic	0.8804	pathogenic	-0.52	Destabilizing	0.072	N	0.507	neutral	None	None	None	None	N
M/F	0.3252	likely_benign	0.3407	ambiguous	-0.542	Destabilizing	0.072	N	0.358	neutral	None	None	None	None	N
M/G	0.8143	likely_pathogenic	0.8263	pathogenic	-2.214	Highly Destabilizing	0.072	N	0.54	neutral	None	None	None	None	N
M/H	0.8023	likely_pathogenic	0.8082	pathogenic	-1.208	Destabilizing	0.628	D	0.542	neutral	None	None	None	None	N
M/I	0.2041	likely_benign	0.2223	benign	-0.769	Destabilizing	None	N	0.122	neutral	N	0.366637767	None	None	N
M/K	0.7047	likely_pathogenic	0.6646	pathogenic	-0.797	Destabilizing	0.055	N	0.483	neutral	N	0.488697399	None	None	N
M/L	0.1253	likely_benign	0.1275	benign	-0.769	Destabilizing	0.001	N	0.202	neutral	N	0.358786288	None	None	N
M/N	0.8157	likely_pathogenic	0.8018	pathogenic	-0.92	Destabilizing	0.072	N	0.54	neutral	None	None	None	None	N
M/P	0.9773	likely_pathogenic	0.9778	pathogenic	-1.096	Destabilizing	0.136	N	0.563	neutral	None	None	None	None	N
M/Q	0.6312	likely_pathogenic	0.5823	pathogenic	-0.816	Destabilizing	0.356	N	0.441	neutral	None	None	None	None	N
M/R	0.6913	likely_pathogenic	0.6722	pathogenic	-0.48	Destabilizing	0.106	N	0.529	neutral	N	0.477749687	None	None	N
M/S	0.7135	likely_pathogenic	0.72	pathogenic	-1.577	Destabilizing	0.016	N	0.436	neutral	None	None	None	None	N
M/T	0.4905	ambiguous	0.4796	ambiguous	-1.325	Destabilizing	None	N	0.327	neutral	N	0.423280484	None	None	N
M/V	0.1104	likely_benign	0.1146	benign	-1.096	Destabilizing	0.001	N	0.279	neutral	N	0.373328879	None	None	N
M/W	0.7786	likely_pathogenic	0.7939	pathogenic	-0.568	Destabilizing	0.864	D	0.534	neutral	None	None	None	None	N
M/Y	0.6686	likely_pathogenic	0.6981	pathogenic	-0.586	Destabilizing	0.356	N	0.538	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.