TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6423	19492;19493;19494	chr2:178728659;178728658;178728657	chr2:179593386;179593385;179593384
N2AB	6106	18541;18542;18543	chr2:178728659;178728658;178728657	chr2:179593386;179593385;179593384
N2A	5179	15760;15761;15762	chr2:178728659;178728658;178728657	chr2:179593386;179593385;179593384
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-48
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.5697
• 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
K/E	rs771317701	0.511	0.013	N	0.239	0.24	0.323886383625	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
K/E	rs771317701	0.511	0.013	N	0.239	0.24	0.323886383625	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	2.77716E-05	None	0	0	0	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
K/A	0.5082	ambiguous	0.4071	ambiguous	0.048	Stabilizing	0.575	D	0.477	neutral	None	None	None	None	N
K/C	0.7468	likely_pathogenic	0.6911	pathogenic	-0.3	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	N
K/D	0.7099	likely_pathogenic	0.5426	ambiguous	-0.033	Destabilizing	0.404	N	0.441	neutral	None	None	None	None	N
K/E	0.2252	likely_benign	0.1415	benign	-0.023	Destabilizing	0.013	N	0.239	neutral	N	0.513182917	None	None	N
K/F	0.7692	likely_pathogenic	0.6639	pathogenic	-0.155	Destabilizing	0.906	D	0.598	neutral	None	None	None	None	N
K/G	0.6289	likely_pathogenic	0.5276	ambiguous	-0.142	Destabilizing	0.575	D	0.436	neutral	None	None	None	None	N
K/H	0.3044	likely_benign	0.2609	benign	-0.325	Destabilizing	0.973	D	0.486	neutral	None	None	None	None	N
K/I	0.343	ambiguous	0.2457	benign	0.471	Stabilizing	0.879	D	0.604	neutral	N	0.489241636	None	None	N
K/L	0.4043	ambiguous	0.3134	benign	0.471	Stabilizing	0.826	D	0.439	neutral	None	None	None	None	N
K/M	0.2774	likely_benign	0.2123	benign	0.118	Stabilizing	0.991	D	0.496	neutral	None	None	None	None	N
K/N	0.4637	ambiguous	0.3146	benign	0.096	Stabilizing	0.782	D	0.395	neutral	N	0.505931658	None	None	N
K/P	0.9526	likely_pathogenic	0.9397	pathogenic	0.357	Stabilizing	0.906	D	0.479	neutral	None	None	None	None	N
K/Q	0.12	likely_benign	0.0998	benign	-0.032	Destabilizing	0.782	D	0.439	neutral	N	0.483918803	None	None	N
K/R	0.0732	likely_benign	0.076	benign	-0.086	Destabilizing	0.003	N	0.222	neutral	N	0.459524578	None	None	N
K/S	0.5021	ambiguous	0.3902	ambiguous	-0.334	Destabilizing	0.575	D	0.446	neutral	None	None	None	None	N
K/T	0.2539	likely_benign	0.1895	benign	-0.18	Destabilizing	0.782	D	0.422	neutral	D	0.533232902	None	None	N
K/V	0.3409	ambiguous	0.2522	benign	0.357	Stabilizing	0.826	D	0.514	neutral	None	None	None	None	N
K/W	0.7456	likely_pathogenic	0.7052	pathogenic	-0.218	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	N
K/Y	0.6184	likely_pathogenic	0.5244	ambiguous	0.135	Stabilizing	0.906	D	0.559	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.