TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6274	19045;19046;19047	chr2:178729336;178729335;178729334	chr2:179594063;179594062;179594061
N2AB	5957	18094;18095;18096	chr2:178729336;178729335;178729334	chr2:179594063;179594062;179594061
N2A	5030	15313;15314;15315	chr2:178729336;178729335;178729334	chr2:179594063;179594062;179594061
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-46
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.233
• 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
S/P	None	None	0.497	N	0.523	0.353	0.126345400529	gnomAD-4.0.0	2.05339E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79958E-06	1.15969E-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
S/A	0.0707	likely_benign	0.0784	benign	-0.85	Destabilizing	None	N	0.169	neutral	N	0.479494418	None	None	N
S/C	0.1522	likely_benign	0.156	benign	-0.746	Destabilizing	0.883	D	0.584	neutral	N	0.504699319	None	None	N
S/D	0.5038	ambiguous	0.5256	ambiguous	-0.799	Destabilizing	0.272	N	0.517	neutral	None	None	None	None	N
S/E	0.4828	ambiguous	0.5137	ambiguous	-0.794	Destabilizing	0.272	N	0.466	neutral	None	None	None	None	N
S/F	0.1988	likely_benign	0.1917	benign	-1.121	Destabilizing	0.667	D	0.688	prob.neutral	N	0.512569629	None	None	N
S/G	0.1203	likely_benign	0.1273	benign	-1.089	Destabilizing	0.072	N	0.431	neutral	None	None	None	None	N
S/H	0.3217	likely_benign	0.3336	benign	-1.579	Destabilizing	0.968	D	0.582	neutral	None	None	None	None	N
S/I	0.2241	likely_benign	0.2187	benign	-0.316	Destabilizing	0.567	D	0.619	neutral	None	None	None	None	N
S/K	0.522	ambiguous	0.5438	ambiguous	-0.804	Destabilizing	0.272	N	0.469	neutral	None	None	None	None	N
S/L	0.1088	likely_benign	0.1073	benign	-0.316	Destabilizing	0.157	N	0.622	neutral	None	None	None	None	N
S/M	0.2057	likely_benign	0.2196	benign	0.046	Stabilizing	0.909	D	0.589	neutral	None	None	None	None	N
S/N	0.1918	likely_benign	0.195	benign	-0.88	Destabilizing	0.431	N	0.523	neutral	None	None	None	None	N
S/P	0.8907	likely_pathogenic	0.9096	pathogenic	-0.461	Destabilizing	0.497	N	0.523	neutral	N	0.515802135	None	None	N
S/Q	0.398	ambiguous	0.4297	ambiguous	-1.095	Destabilizing	0.726	D	0.538	neutral	None	None	None	None	N
S/R	0.4124	ambiguous	0.4208	ambiguous	-0.638	Destabilizing	0.567	D	0.527	neutral	None	None	None	None	N
S/T	0.0812	likely_benign	0.0858	benign	-0.856	Destabilizing	0.055	N	0.448	neutral	N	0.462522024	None	None	N
S/V	0.1934	likely_benign	0.2095	benign	-0.461	Destabilizing	0.157	N	0.623	neutral	None	None	None	None	N
S/W	0.3225	likely_benign	0.3144	benign	-1.084	Destabilizing	0.968	D	0.75	deleterious	None	None	None	None	N
S/Y	0.1907	likely_benign	0.1892	benign	-0.804	Destabilizing	0.667	D	0.695	prob.neutral	N	0.49769788	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.