TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14293	43102;43103;43104	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
N2AB	12652	38179;38180;38181	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
N2A	11725	35398;35399;35400	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
N2B	5228	15907;15908;15909	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
Novex-1	5353	16282;16283;16284	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
Novex-2	5420	16483;16484;16485	chr2:178633482;178633481;178633480	chr2:179498209;179498208;179498207
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-93
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.3418
• 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/I	None	None	0.213	N	0.218	0.03	0.104622674875	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.1324	likely_benign	0.1644	benign	-1.11	Destabilizing	0.228	N	0.29	neutral	None	None	None	None	N
L/C	0.5504	ambiguous	0.4831	ambiguous	-0.526	Destabilizing	0.983	D	0.33	neutral	None	None	None	None	N
L/D	0.3517	ambiguous	0.4444	ambiguous	-0.712	Destabilizing	None	N	0.174	neutral	None	None	None	None	N
L/E	0.1932	likely_benign	0.237	benign	-0.794	Destabilizing	None	N	0.174	neutral	None	None	None	None	N
L/F	0.1464	likely_benign	0.1054	benign	-1.004	Destabilizing	0.002	N	0.231	neutral	N	0.45558964	None	None	N
L/G	0.2827	likely_benign	0.3334	benign	-1.331	Destabilizing	0.228	N	0.301	neutral	None	None	None	None	N
L/H	0.2101	likely_benign	0.204	benign	-0.625	Destabilizing	0.794	D	0.429	neutral	N	0.499611273	None	None	N
L/I	0.0791	likely_benign	0.0739	benign	-0.622	Destabilizing	0.213	N	0.218	neutral	N	0.455167449	None	None	N
L/K	0.1908	likely_benign	0.2037	benign	-0.694	Destabilizing	0.004	N	0.191	neutral	None	None	None	None	N
L/M	0.0979	likely_benign	0.1024	benign	-0.395	Destabilizing	0.836	D	0.319	neutral	None	None	None	None	N
L/N	0.1671	likely_benign	0.2126	benign	-0.326	Destabilizing	0.004	N	0.245	neutral	None	None	None	None	N
L/P	0.1556	likely_benign	0.1803	benign	-0.752	Destabilizing	0.523	D	0.456	neutral	N	0.43735418	None	None	N
L/Q	0.1173	likely_benign	0.1309	benign	-0.605	Destabilizing	0.264	N	0.392	neutral	None	None	None	None	N
L/R	0.2039	likely_benign	0.1879	benign	-0.044	Destabilizing	0.213	N	0.339	neutral	N	0.44974548	None	None	N
L/S	0.1462	likely_benign	0.161	benign	-0.794	Destabilizing	0.228	N	0.244	neutral	None	None	None	None	N
L/T	0.122	likely_benign	0.146	benign	-0.773	Destabilizing	0.228	N	0.307	neutral	None	None	None	None	N
L/V	0.082	likely_benign	0.0866	benign	-0.752	Destabilizing	0.101	N	0.225	neutral	N	0.447389418	None	None	N
L/W	0.3014	likely_benign	0.243	benign	-1.014	Destabilizing	0.983	D	0.391	neutral	None	None	None	None	N
L/Y	0.3026	likely_benign	0.2554	benign	-0.796	Destabilizing	0.264	N	0.386	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.