TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29368	88327;88328;88329	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
N2AB	27727	83404;83405;83406	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
N2A	26800	80623;80624;80625	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
N2B	20303	61132;61133;61134	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
Novex-1	20428	61507;61508;61509	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
Novex-2	20495	61708;61709;61710	chr2:178557052;178557051;178557050	chr2:179421779;179421778;179421777
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: Fn3-102
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3204
• 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/I	rs757375731	-0.25	0.997	N	0.788	0.403	0.39724302092	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.63506E-04	None	0	0	0
T/I	rs757375731	-0.25	0.997	N	0.788	0.403	0.39724302092	gnomAD-4.0.0	7.52672E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.27545E-04	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	0.2279	likely_benign	0.1638	benign	-0.798	Destabilizing	0.977	D	0.464	neutral	N	0.509226817	None	None	I
T/C	0.6917	likely_pathogenic	0.6045	pathogenic	-0.46	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
T/D	0.8529	likely_pathogenic	0.7625	pathogenic	-0.561	Destabilizing	0.995	D	0.663	neutral	None	None	None	None	I
T/E	0.7678	likely_pathogenic	0.6463	pathogenic	-0.576	Destabilizing	0.966	D	0.617	neutral	None	None	None	None	I
T/F	0.6695	likely_pathogenic	0.5234	ambiguous	-0.985	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	I
T/G	0.6383	likely_pathogenic	0.5425	ambiguous	-1.034	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	I
T/H	0.6875	likely_pathogenic	0.5681	pathogenic	-1.379	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
T/I	0.275	likely_benign	0.215	benign	-0.263	Destabilizing	0.997	D	0.788	deleterious	N	0.517521584	None	None	I
T/K	0.6126	likely_pathogenic	0.4831	ambiguous	-0.758	Destabilizing	0.235	N	0.318	neutral	N	0.49127392	None	None	I
T/L	0.2228	likely_benign	0.1781	benign	-0.263	Destabilizing	0.983	D	0.551	neutral	None	None	None	None	I
T/M	0.1581	likely_benign	0.1262	benign	0.206	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
T/N	0.3908	ambiguous	0.2991	benign	-0.709	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	I
T/P	0.6877	likely_pathogenic	0.608	pathogenic	-0.41	Destabilizing	0.997	D	0.787	deleterious	D	0.535853448	None	None	I
T/Q	0.5831	likely_pathogenic	0.4752	ambiguous	-0.959	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	I
T/R	0.5369	ambiguous	0.3896	ambiguous	-0.455	Destabilizing	0.987	D	0.661	neutral	N	0.492034388	None	None	I
T/S	0.2687	likely_benign	0.2034	benign	-0.941	Destabilizing	0.977	D	0.427	neutral	D	0.525370276	None	None	I
T/V	0.2157	likely_benign	0.1686	benign	-0.41	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	I
T/W	0.9072	likely_pathogenic	0.8522	pathogenic	-0.92	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
T/Y	0.7424	likely_pathogenic	0.6262	pathogenic	-0.679	Destabilizing	0.999	D	0.83	deleterious	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.