TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9108	27547;27548;27549	chr2:178712703;178712702;178712701	chr2:179577430;179577429;179577428
N2AB	8791	26596;26597;26598	chr2:178712703;178712702;178712701	chr2:179577430;179577429;179577428
N2A	7864	23815;23816;23817	chr2:178712703;178712702;178712701	chr2:179577430;179577429;179577428
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-76
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4208
• 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
I/L	None	None	0.002	N	0.161	0.081	0.214338557667	gnomAD-4.0.0	1.59439E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86648E-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
I/A	0.5336	ambiguous	0.4932	ambiguous	-2.337	Highly Destabilizing	0.016	N	0.304	neutral	None	None	None	None	N
I/C	0.7711	likely_pathogenic	0.7574	pathogenic	-2.007	Highly Destabilizing	0.356	N	0.346	neutral	None	None	None	None	N
I/D	0.9678	likely_pathogenic	0.9625	pathogenic	-2.65	Highly Destabilizing	0.356	N	0.405	neutral	None	None	None	None	N
I/E	0.9349	likely_pathogenic	0.9279	pathogenic	-2.544	Highly Destabilizing	0.136	N	0.389	neutral	None	None	None	None	N
I/F	0.6304	likely_pathogenic	0.6162	pathogenic	-1.598	Destabilizing	None	N	0.164	neutral	None	None	None	None	N
I/G	0.833	likely_pathogenic	0.8007	pathogenic	-2.741	Highly Destabilizing	0.136	N	0.372	neutral	None	None	None	None	N
I/H	0.9355	likely_pathogenic	0.9243	pathogenic	-1.957	Destabilizing	0.864	D	0.368	neutral	None	None	None	None	N
I/K	0.9097	likely_pathogenic	0.9056	pathogenic	-1.688	Destabilizing	0.106	N	0.387	neutral	N	0.482131389	None	None	N
I/L	0.2572	likely_benign	0.2419	benign	-1.224	Destabilizing	0.002	N	0.161	neutral	N	0.50390642	None	None	N
I/M	0.2377	likely_benign	0.2204	benign	-1.3	Destabilizing	0.171	N	0.379	neutral	N	0.463773644	None	None	N
I/N	0.7458	likely_pathogenic	0.7252	pathogenic	-1.83	Destabilizing	0.628	D	0.397	neutral	None	None	None	None	N
I/P	0.8644	likely_pathogenic	0.8691	pathogenic	-1.572	Destabilizing	0.356	N	0.405	neutral	None	None	None	None	N
I/Q	0.8923	likely_pathogenic	0.8758	pathogenic	-1.931	Destabilizing	0.628	D	0.386	neutral	None	None	None	None	N
I/R	0.8641	likely_pathogenic	0.8533	pathogenic	-1.184	Destabilizing	0.295	N	0.397	neutral	N	0.482131389	None	None	N
I/S	0.5941	likely_pathogenic	0.5636	ambiguous	-2.476	Highly Destabilizing	0.072	N	0.362	neutral	None	None	None	None	N
I/T	0.4118	ambiguous	0.391	ambiguous	-2.248	Highly Destabilizing	0.029	N	0.291	neutral	N	0.470014615	None	None	N
I/V	0.0559	likely_benign	0.0554	benign	-1.572	Destabilizing	None	N	0.125	neutral	N	0.314562137	None	None	N
I/W	0.979	likely_pathogenic	0.9773	pathogenic	-1.785	Destabilizing	0.864	D	0.379	neutral	None	None	None	None	N
I/Y	0.9169	likely_pathogenic	0.9136	pathogenic	-1.536	Destabilizing	0.038	N	0.35	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.