TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6717	20374;20375;20376	chr2:178727216;178727215;178727214	chr2:179591943;179591942;179591941
N2AB	6400	19423;19424;19425	chr2:178727216;178727215;178727214	chr2:179591943;179591942;179591941
N2A	5473	16642;16643;16644	chr2:178727216;178727215;178727214	chr2:179591943;179591942;179591941
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-51
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.5265
• 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
T/I	None	None	0.117	N	0.369	0.246	0.473774312618	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	rs1468330606	-0.391	None	N	0.093	0.061	0.26547132957	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/S	rs1468330606	-0.391	None	N	0.093	0.061	0.26547132957	gnomAD-4.0.0	4.10663E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39824E-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	0.0761	likely_benign	0.0739	benign	-0.452	Destabilizing	None	N	0.08	neutral	N	0.492039641	None	None	N
T/C	0.5332	ambiguous	0.4933	ambiguous	-0.36	Destabilizing	0.824	D	0.394	neutral	None	None	None	None	N
T/D	0.2346	likely_benign	0.2623	benign	0.035	Stabilizing	0.149	N	0.328	neutral	None	None	None	None	N
T/E	0.2476	likely_benign	0.2724	benign	0.024	Stabilizing	0.081	N	0.315	neutral	None	None	None	None	N
T/F	0.2141	likely_benign	0.2204	benign	-0.609	Destabilizing	0.001	N	0.283	neutral	None	None	None	None	N
T/G	0.2122	likely_benign	0.2124	benign	-0.682	Destabilizing	0.035	N	0.345	neutral	None	None	None	None	N
T/H	0.2188	likely_benign	0.2284	benign	-0.906	Destabilizing	0.555	D	0.433	neutral	None	None	None	None	N
T/I	0.1915	likely_benign	0.1958	benign	0.057	Stabilizing	0.117	N	0.369	neutral	N	0.520266392	None	None	N
T/K	0.2499	likely_benign	0.2705	benign	-0.558	Destabilizing	0.081	N	0.304	neutral	None	None	None	None	N
T/L	0.1113	likely_benign	0.1107	benign	0.057	Stabilizing	0.035	N	0.311	neutral	None	None	None	None	N
T/M	0.0995	likely_benign	0.0988	benign	0.05	Stabilizing	0.555	D	0.398	neutral	None	None	None	None	N
T/N	0.0878	likely_benign	0.0922	benign	-0.478	Destabilizing	0.062	N	0.286	neutral	N	0.52172783	None	None	N
T/P	0.5372	ambiguous	0.5639	ambiguous	-0.08	Destabilizing	0.317	N	0.399	neutral	D	0.529251235	None	None	N
T/Q	0.2152	likely_benign	0.2246	benign	-0.579	Destabilizing	0.38	N	0.412	neutral	None	None	None	None	N
T/R	0.2093	likely_benign	0.2235	benign	-0.338	Destabilizing	0.38	N	0.409	neutral	None	None	None	None	N
T/S	0.0745	likely_benign	0.0761	benign	-0.693	Destabilizing	None	N	0.093	neutral	N	0.403977939	None	None	N
T/V	0.1595	likely_benign	0.1535	benign	-0.08	Destabilizing	0.081	N	0.229	neutral	None	None	None	None	N
T/W	0.5764	likely_pathogenic	0.5881	pathogenic	-0.638	Destabilizing	0.935	D	0.457	neutral	None	None	None	None	N
T/Y	0.235	likely_benign	0.2421	benign	-0.367	Destabilizing	0.235	N	0.444	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.