TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15186	45781;45782;45783	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
N2AB	13545	40858;40859;40860	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
N2A	12618	38077;38078;38079	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
N2B	6121	18586;18587;18588	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
Novex-1	6246	18961;18962;18963	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
Novex-2	6313	19162;19163;19164	chr2:178621162;178621161;178621160	chr2:179485889;179485888;179485887
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: Ig-103
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.3385
• 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	rs878910401	None	0.002	N	0.127	0.257	None	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.274	likely_benign	0.2397	benign	-1.776	Destabilizing	0.001	N	0.123	neutral	None	None	None	None	N
M/C	0.8274	likely_pathogenic	0.732	pathogenic	-1.259	Destabilizing	0.968	D	0.465	neutral	None	None	None	None	N
M/D	0.7838	likely_pathogenic	0.7515	pathogenic	-0.62	Destabilizing	0.111	N	0.284	neutral	None	None	None	None	N
M/E	0.2823	likely_benign	0.2868	benign	-0.603	Destabilizing	0.001	N	0.181	neutral	None	None	None	None	N
M/F	0.6013	likely_pathogenic	0.549	ambiguous	-0.856	Destabilizing	0.738	D	0.425	neutral	None	None	None	None	N
M/G	0.5707	likely_pathogenic	0.4944	ambiguous	-2.078	Highly Destabilizing	0.001	N	0.262	neutral	None	None	None	None	N
M/H	0.6399	likely_pathogenic	0.5968	pathogenic	-1.109	Destabilizing	0.908	D	0.55	neutral	None	None	None	None	N
M/I	0.4184	ambiguous	0.4123	ambiguous	-1.001	Destabilizing	0.302	N	0.365	neutral	N	0.481799312	None	None	N
M/K	0.1755	likely_benign	0.1656	benign	-0.584	Destabilizing	0.086	N	0.255	neutral	N	0.479078255	None	None	N
M/L	0.2466	likely_benign	0.22	benign	-1.001	Destabilizing	0.039	N	0.25	neutral	N	0.44767135	None	None	N
M/N	0.4673	ambiguous	0.4273	ambiguous	-0.421	Destabilizing	0.365	N	0.335	neutral	None	None	None	None	N
M/P	0.9473	likely_pathogenic	0.9349	pathogenic	-1.233	Destabilizing	0.538	D	0.409	neutral	None	None	None	None	N
M/Q	0.1937	likely_benign	0.1856	benign	-0.537	Destabilizing	0.223	N	0.345	neutral	None	None	None	None	N
M/R	0.2149	likely_benign	0.195	benign	-0.06	Destabilizing	0.302	N	0.407	neutral	N	0.462554861	None	None	N
M/S	0.3029	likely_benign	0.2641	benign	-1.038	Destabilizing	0.051	N	0.257	neutral	None	None	None	None	N
M/T	0.1328	likely_benign	0.1243	benign	-0.913	Destabilizing	0.002	N	0.127	neutral	N	0.418439716	None	None	N
M/V	0.1088	likely_benign	0.1079	benign	-1.233	Destabilizing	0.086	N	0.266	neutral	N	0.465731854	None	None	N
M/W	0.8546	likely_pathogenic	0.8301	pathogenic	-0.769	Destabilizing	0.968	D	0.467	neutral	None	None	None	None	N
M/Y	0.7868	likely_pathogenic	0.7409	pathogenic	-0.797	Destabilizing	0.896	D	0.559	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.