TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29191	87796;87797;87798	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
N2AB	27550	82873;82874;82875	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
N2A	26623	80092;80093;80094	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
N2B	20126	60601;60602;60603	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
Novex-1	20251	60976;60977;60978	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
Novex-2	20318	61177;61178;61179	chr2:178557783;178557782;178557781	chr2:179422510;179422509;179422508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-100
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.6127
• Predicted PPI site: I

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
T/A	rs963739938	None	0.011	N	0.139	0.081	0.154104182512	gnomAD-4.0.0	6.84162E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99429E-06	0	0
T/I	rs757571814	0.024	0.968	N	0.512	0.349	0.541330971987	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
T/I	rs757571814	0.024	0.968	N	0.512	0.349	0.541330971987	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85786E-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
T/A	0.0724	likely_benign	0.0832	benign	-0.313	Destabilizing	0.011	N	0.139	neutral	N	0.471034358	None	None	I
T/C	0.5462	ambiguous	0.6134	pathogenic	-0.181	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
T/D	0.8277	likely_pathogenic	0.8472	pathogenic	0.033	Stabilizing	0.988	D	0.513	neutral	None	None	None	None	I
T/E	0.7938	likely_pathogenic	0.8206	pathogenic	-0.061	Destabilizing	0.919	D	0.515	neutral	None	None	None	None	I
T/F	0.5958	likely_pathogenic	0.6313	pathogenic	-0.901	Destabilizing	0.988	D	0.597	neutral	None	None	None	None	I
T/G	0.2936	likely_benign	0.3393	benign	-0.406	Destabilizing	0.851	D	0.48	neutral	None	None	None	None	I
T/H	0.6099	likely_pathogenic	0.6316	pathogenic	-0.698	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	I
T/I	0.5781	likely_pathogenic	0.6352	pathogenic	-0.191	Destabilizing	0.968	D	0.512	neutral	N	0.469838302	None	None	I
T/K	0.6967	likely_pathogenic	0.6793	pathogenic	-0.276	Destabilizing	0.896	D	0.518	neutral	N	0.510475394	None	None	I
T/L	0.2174	likely_benign	0.2421	benign	-0.191	Destabilizing	0.919	D	0.523	neutral	None	None	None	None	I
T/M	0.1285	likely_benign	0.1443	benign	0.068	Stabilizing	0.999	D	0.556	neutral	None	None	None	None	I
T/N	0.2815	likely_benign	0.3075	benign	-0.033	Destabilizing	0.988	D	0.497	neutral	None	None	None	None	I
T/P	0.3549	ambiguous	0.5112	ambiguous	-0.205	Destabilizing	0.984	D	0.516	neutral	N	0.505258788	None	None	I
T/Q	0.55	ambiguous	0.5689	pathogenic	-0.315	Destabilizing	0.988	D	0.555	neutral	None	None	None	None	I
T/R	0.5966	likely_pathogenic	0.5983	pathogenic	0.034	Stabilizing	0.984	D	0.547	neutral	N	0.505397648	None	None	I
T/S	0.1473	likely_benign	0.1736	benign	-0.224	Destabilizing	0.64	D	0.511	neutral	N	0.457910346	None	None	I
T/V	0.2962	likely_benign	0.3564	ambiguous	-0.205	Destabilizing	0.851	D	0.495	neutral	None	None	None	None	I
T/W	0.9094	likely_pathogenic	0.9179	pathogenic	-0.912	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
T/Y	0.6863	likely_pathogenic	0.711	pathogenic	-0.619	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	I

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.