TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35726	107401;107402;107403	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
N2AB	34085	102478;102479;102480	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
N2A	33158	99697;99698;99699	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
N2B	26661	80206;80207;80208	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
Novex-1	26786	80581;80582;80583	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
Novex-2	26853	80782;80783;80784	chr2:178528575;178528574;178528573	chr2:179393302;179393301;179393300
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-168
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5438
• 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/T	None	None	None	N	0.093	0.063	0.137902524267	gnomAD-4.0.0	6.84712E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99964E-07	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
S/A	0.0871	likely_benign	0.0886	benign	-0.473	Destabilizing	0.016	N	0.194	neutral	None	None	None	None	N
S/C	0.1805	likely_benign	0.2546	benign	-0.327	Destabilizing	0.78	D	0.317	neutral	N	0.508675791	None	None	N
S/D	0.5442	ambiguous	0.5338	ambiguous	-0.004	Destabilizing	0.081	N	0.252	neutral	None	None	None	None	N
S/E	0.5814	likely_pathogenic	0.5631	ambiguous	-0.019	Destabilizing	0.149	N	0.242	neutral	None	None	None	None	N
S/F	0.2192	likely_benign	0.2263	benign	-0.677	Destabilizing	0.555	D	0.438	neutral	None	None	None	None	N
S/G	0.1423	likely_benign	0.1454	benign	-0.709	Destabilizing	None	N	0.087	neutral	N	0.501160556	None	None	N
S/H	0.4104	ambiguous	0.4146	ambiguous	-1.121	Destabilizing	0.38	N	0.339	neutral	None	None	None	None	N
S/I	0.1831	likely_benign	0.1806	benign	0.041	Stabilizing	0.062	N	0.391	neutral	D	0.525517496	None	None	N
S/K	0.6718	likely_pathogenic	0.639	pathogenic	-0.649	Destabilizing	0.081	N	0.245	neutral	None	None	None	None	N
S/L	0.1038	likely_benign	0.1104	benign	0.041	Stabilizing	0.035	N	0.367	neutral	None	None	None	None	N
S/M	0.2167	likely_benign	0.2306	benign	0.155	Stabilizing	0.555	D	0.341	neutral	None	None	None	None	N
S/N	0.1949	likely_benign	0.1922	benign	-0.52	Destabilizing	None	N	0.129	neutral	N	0.52182383	None	None	N
S/P	0.7207	likely_pathogenic	0.742	pathogenic	-0.096	Destabilizing	0.555	D	0.405	neutral	None	None	None	None	N
S/Q	0.5469	ambiguous	0.5399	ambiguous	-0.623	Destabilizing	0.38	N	0.381	neutral	None	None	None	None	N
S/R	0.5328	ambiguous	0.5126	ambiguous	-0.524	Destabilizing	0.317	N	0.403	neutral	N	0.519244885	None	None	N
S/T	0.069	likely_benign	0.0711	benign	-0.533	Destabilizing	None	N	0.093	neutral	N	0.460561941	None	None	N
S/V	0.209	likely_benign	0.2121	benign	-0.096	Destabilizing	0.002	N	0.295	neutral	None	None	None	None	N
S/W	0.3765	ambiguous	0.4166	ambiguous	-0.713	Destabilizing	0.935	D	0.468	neutral	None	None	None	None	N
S/Y	0.2318	likely_benign	0.2349	benign	-0.434	Destabilizing	0.555	D	0.425	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.