TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9965	30118;30119;30120	chr2:178704579;178704578;178704577	chr2:179569306;179569305;179569304
N2AB	9648	29167;29168;29169	chr2:178704579;178704578;178704577	chr2:179569306;179569305;179569304
N2A	8721	26386;26387;26388	chr2:178704579;178704578;178704577	chr2:179569306;179569305;179569304
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-84
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.4565
• 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/F	None	None	0.56	None	0.227	0.115	0.38225645794	gnomAD-4.0.0	8.40227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18753E-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
L/A	0.1685	likely_benign	0.2091	benign	-1.081	Destabilizing	None	N	0.125	neutral	None	None	None	None	N
L/C	0.6463	likely_pathogenic	0.7159	pathogenic	-0.582	Destabilizing	0.864	D	0.227	neutral	None	None	None	None	N
L/D	0.5196	ambiguous	0.6005	pathogenic	-0.698	Destabilizing	0.072	N	0.351	neutral	None	None	None	None	N
L/E	0.2178	likely_benign	0.2562	benign	-0.773	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	N
L/F	0.2063	likely_benign	0.2197	benign	-0.925	Destabilizing	0.56	D	0.227	neutral	None	None	None	None	N
L/G	0.4423	ambiguous	0.5091	ambiguous	-1.303	Destabilizing	0.072	N	0.323	neutral	None	None	None	None	N
L/H	0.2364	likely_benign	0.2702	benign	-0.56	Destabilizing	0.828	D	0.275	neutral	None	None	None	None	N
L/I	0.1037	likely_benign	0.1055	benign	-0.591	Destabilizing	0.055	N	0.215	neutral	None	None	None	None	N
L/K	0.1823	likely_benign	0.2112	benign	-0.721	Destabilizing	0.072	N	0.307	neutral	None	None	None	None	N
L/M	0.135	likely_benign	0.1455	benign	-0.437	Destabilizing	0.628	D	0.26	neutral	None	None	None	None	N
L/N	0.3149	likely_benign	0.3723	ambiguous	-0.399	Destabilizing	0.072	N	0.363	neutral	None	None	None	None	N
L/P	0.0941	likely_benign	0.1149	benign	-0.722	Destabilizing	None	N	0.19	neutral	None	None	None	None	N
L/Q	0.1194	likely_benign	0.1358	benign	-0.662	Destabilizing	0.356	N	0.321	neutral	None	None	None	None	N
L/R	0.1659	likely_benign	0.1875	benign	-0.069	Destabilizing	0.295	N	0.327	neutral	None	None	None	None	N
L/S	0.2189	likely_benign	0.258	benign	-0.864	Destabilizing	0.003	N	0.183	neutral	None	None	None	None	N
L/T	0.1761	likely_benign	0.2	benign	-0.835	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
L/V	0.1063	likely_benign	0.1103	benign	-0.722	Destabilizing	0.024	N	0.245	neutral	None	None	None	None	N
L/W	0.3224	likely_benign	0.3529	ambiguous	-0.938	Destabilizing	0.864	D	0.304	neutral	None	None	None	None	N
L/Y	0.3881	ambiguous	0.4461	ambiguous	-0.725	Destabilizing	0.628	D	0.238	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.