TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33526	100801;100802;100803	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
N2AB	31885	95878;95879;95880	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
N2A	30958	93097;93098;93099	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
N2B	24461	73606;73607;73608	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
Novex-1	24586	73981;73982;73983	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
Novex-2	24653	74182;74183;74184	chr2:178536171;178536170;178536169	chr2:179400898;179400897;179400896
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-158
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6095
• 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
I/M	None	None	0.088	N	0.497	0.078	0.149567049428	gnomAD-4.0.0	1.36866E-06	None	None	None	None	I	None	5.97693E-05	0	None	0	0	None	0	0	0	0	0
I/T	None	None	None	N	0.226	0.178	0.475971816791	gnomAD-4.0.0	1.59176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85904E-06	0	0
I/V	None	None	None	N	0.129	0.108	0.141422826196	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	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
I/A	0.2187	likely_benign	0.2255	benign	-0.813	Destabilizing	0.011	N	0.349	neutral	None	None	None	None	I
I/C	0.6889	likely_pathogenic	0.7397	pathogenic	-0.533	Destabilizing	0.46	N	0.51	neutral	None	None	None	None	I
I/D	0.6744	likely_pathogenic	0.7312	pathogenic	-0.616	Destabilizing	0.107	N	0.587	neutral	None	None	None	None	I
I/E	0.5552	ambiguous	0.5721	pathogenic	-0.696	Destabilizing	0.081	N	0.571	neutral	None	None	None	None	I
I/F	0.2302	likely_benign	0.2554	benign	-0.735	Destabilizing	0.112	N	0.487	neutral	N	0.513798993	None	None	I
I/G	0.6124	likely_pathogenic	0.6608	pathogenic	-1.009	Destabilizing	0.107	N	0.519	neutral	None	None	None	None	I
I/H	0.5238	ambiguous	0.5947	pathogenic	-0.315	Destabilizing	0.802	D	0.517	neutral	None	None	None	None	I
I/K	0.434	ambiguous	0.4614	ambiguous	-0.581	Destabilizing	0.004	N	0.571	neutral	None	None	None	None	I
I/L	0.1217	likely_benign	0.1286	benign	-0.402	Destabilizing	None	N	0.121	neutral	N	0.451326382	None	None	I
I/M	0.1008	likely_benign	0.1104	benign	-0.404	Destabilizing	0.088	N	0.497	neutral	N	0.495039874	None	None	I
I/N	0.2296	likely_benign	0.2595	benign	-0.312	Destabilizing	0.241	N	0.577	neutral	N	0.452961178	None	None	I
I/P	0.9233	likely_pathogenic	0.9275	pathogenic	-0.506	Destabilizing	0.46	N	0.572	neutral	None	None	None	None	I
I/Q	0.424	ambiguous	0.4573	ambiguous	-0.553	Destabilizing	0.261	N	0.553	neutral	None	None	None	None	I
I/R	0.3807	ambiguous	0.4214	ambiguous	0.025	Stabilizing	0.253	N	0.559	neutral	None	None	None	None	I
I/S	0.2178	likely_benign	0.2384	benign	-0.714	Destabilizing	0.004	N	0.323	neutral	N	0.433391195	None	None	I
I/T	0.122	likely_benign	0.1299	benign	-0.69	Destabilizing	None	N	0.226	neutral	N	0.402628358	None	None	I
I/V	0.0561	likely_benign	0.0602	benign	-0.506	Destabilizing	None	N	0.129	neutral	N	0.425217216	None	None	I
I/W	0.8846	likely_pathogenic	0.9117	pathogenic	-0.776	Destabilizing	0.936	D	0.544	neutral	None	None	None	None	I
I/Y	0.6408	likely_pathogenic	0.6886	pathogenic	-0.541	Destabilizing	0.038	N	0.544	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.