TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23906	71941;71942;71943	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
N2AB	22265	67018;67019;67020	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
N2A	21338	64237;64238;64239	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
N2B	14841	44746;44747;44748	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
Novex-1	14966	45121;45122;45123	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
Novex-2	15033	45322;45323;45324	chr2:178574416;178574415;178574414	chr2:179439143;179439142;179439141
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: Fn3-61
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.617
• 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
M/I	None	None	None	N	0.052	0.15	0.332902724076	gnomAD-4.0.0	6.84324E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99573E-07	0	0
M/T	None	None	0.024	N	0.386	0.264	0.507449927524	gnomAD-4.0.0	5.47444E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19642E-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	0.2503	likely_benign	0.2772	benign	-0.115	Destabilizing	None	N	0.101	neutral	None	None	None	None	I
M/C	0.7198	likely_pathogenic	0.71	pathogenic	-0.389	Destabilizing	0.356	N	0.395	neutral	None	None	None	None	I
M/D	0.8432	likely_pathogenic	0.8783	pathogenic	0.578	Stabilizing	0.136	N	0.47	neutral	None	None	None	None	I
M/E	0.5464	ambiguous	0.6091	pathogenic	0.519	Stabilizing	0.072	N	0.484	neutral	None	None	None	None	I
M/F	0.3579	ambiguous	0.4142	ambiguous	0.036	Stabilizing	0.038	N	0.259	neutral	None	None	None	None	I
M/G	0.6211	likely_pathogenic	0.6791	pathogenic	-0.244	Destabilizing	0.038	N	0.457	neutral	None	None	None	None	I
M/H	0.5109	ambiguous	0.5442	ambiguous	0.465	Stabilizing	0.628	D	0.439	neutral	None	None	None	None	I
M/I	0.1697	likely_benign	0.2276	benign	0.116	Stabilizing	None	N	0.052	neutral	N	0.374257173	None	None	I
M/K	0.1741	likely_benign	0.1921	benign	0.617	Stabilizing	0.055	N	0.417	neutral	N	0.40296114	None	None	I
M/L	0.0809	likely_benign	0.0854	benign	0.116	Stabilizing	None	N	0.057	neutral	N	0.403886647	None	None	I
M/N	0.5079	ambiguous	0.5789	pathogenic	0.682	Stabilizing	0.356	N	0.463	neutral	None	None	None	None	I
M/P	0.7145	likely_pathogenic	0.7629	pathogenic	0.066	Stabilizing	0.136	N	0.459	neutral	None	None	None	None	I
M/Q	0.2719	likely_benign	0.2768	benign	0.544	Stabilizing	0.136	N	0.285	neutral	None	None	None	None	I
M/R	0.186	likely_benign	0.2063	benign	1.029	Stabilizing	0.106	N	0.445	neutral	N	0.438671224	None	None	I
M/S	0.378	ambiguous	0.4363	ambiguous	0.246	Stabilizing	0.016	N	0.376	neutral	None	None	None	None	I
M/T	0.1921	likely_benign	0.2322	benign	0.288	Stabilizing	0.024	N	0.386	neutral	N	0.452888528	None	None	I
M/V	0.0689	likely_benign	0.0782	benign	0.066	Stabilizing	0.002	N	0.222	neutral	N	0.449080219	None	None	I
M/W	0.6597	likely_pathogenic	0.6898	pathogenic	0.009	Stabilizing	0.864	D	0.399	neutral	None	None	None	None	I
M/Y	0.5797	likely_pathogenic	0.6121	pathogenic	0.223	Stabilizing	0.136	N	0.439	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.