TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22972	69139;69140;69141	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
N2AB	21331	64216;64217;64218	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
N2A	20404	61435;61436;61437	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
N2B	13907	41944;41945;41946	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
Novex-1	14032	42319;42320;42321	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
Novex-2	14099	42520;42521;42522	chr2:178577421;178577420;178577419	chr2:179442148;179442147;179442146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-128
• Domain position: 23
• Structural Position: 38
• Q(SASA): 0.5594
• 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
L/P	rs2046677771	None	0.484	N	0.421	0.322	0.74037354781	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96928E-04	0	0	0	None	0	0	0	0	0
L/P	rs2046677771	None	0.484	N	0.421	0.322	0.74037354781	gnomAD-4.0.0	1.97392E-05	None	None	None	None	N	None	0	1.96928E-04	None	0	0	None	0	0	0	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
L/A	0.1171	likely_benign	0.1305	benign	-0.535	Destabilizing	0.035	N	0.301	neutral	None	None	None	None	N
L/C	0.3265	likely_benign	0.3687	ambiguous	-0.785	Destabilizing	0.935	D	0.315	neutral	None	None	None	None	N
L/D	0.4501	ambiguous	0.5124	ambiguous	-0.088	Destabilizing	0.38	N	0.418	neutral	None	None	None	None	N
L/E	0.205	likely_benign	0.2331	benign	-0.167	Destabilizing	0.081	N	0.411	neutral	None	None	None	None	N
L/F	0.0955	likely_benign	0.1062	benign	-0.508	Destabilizing	0.317	N	0.362	neutral	N	0.492615644	None	None	N
L/G	0.309	likely_benign	0.3554	ambiguous	-0.68	Destabilizing	0.149	N	0.414	neutral	None	None	None	None	N
L/H	0.0957	likely_benign	0.1114	benign	0.067	Stabilizing	0.001	N	0.353	neutral	N	0.508507816	None	None	N
L/I	0.0786	likely_benign	0.0769	benign	-0.272	Destabilizing	0.027	N	0.273	neutral	N	0.482051934	None	None	N
L/K	0.1195	likely_benign	0.1299	benign	-0.371	Destabilizing	0.081	N	0.339	neutral	None	None	None	None	N
L/M	0.0999	likely_benign	0.0996	benign	-0.524	Destabilizing	0.555	D	0.387	neutral	None	None	None	None	N
L/N	0.1992	likely_benign	0.2376	benign	-0.284	Destabilizing	0.235	N	0.415	neutral	None	None	None	None	N
L/P	0.7352	likely_pathogenic	0.785	pathogenic	-0.329	Destabilizing	0.484	N	0.421	neutral	N	0.503063023	None	None	N
L/Q	0.0825	likely_benign	0.0892	benign	-0.45	Destabilizing	0.38	N	0.393	neutral	None	None	None	None	N
L/R	0.0888	likely_benign	0.0948	benign	0.124	Stabilizing	None	N	0.279	neutral	N	0.439685236	None	None	N
L/S	0.1197	likely_benign	0.1333	benign	-0.719	Destabilizing	0.081	N	0.344	neutral	None	None	None	None	N
L/T	0.0929	likely_benign	0.0956	benign	-0.69	Destabilizing	0.002	N	0.237	neutral	None	None	None	None	N
L/V	0.0796	likely_benign	0.0778	benign	-0.329	Destabilizing	None	N	0.094	neutral	N	0.470008143	None	None	N
L/W	0.2055	likely_benign	0.2383	benign	-0.533	Destabilizing	0.935	D	0.398	neutral	None	None	None	None	N
L/Y	0.23	likely_benign	0.2588	benign	-0.299	Destabilizing	0.235	N	0.378	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.