TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28370	85333;85334;85335	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
N2AB	26729	80410;80411;80412	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
N2A	25802	77629;77630;77631	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
N2B	19305	58138;58139;58140	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
Novex-1	19430	58513;58514;58515	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
Novex-2	19497	58714;58715;58716	chr2:178561024;178561023;178561022	chr2:179425751;179425750;179425749
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-143
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.6294
• Predicted PPI site: I

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/R	rs1316361788	None	0.025	N	0.299	0.11	0.207176502487	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
K/A	0.5867	likely_pathogenic	0.5256	ambiguous	-0.116	Destabilizing	0.916	D	0.661	neutral	None	None	None	None	I
K/C	0.8017	likely_pathogenic	0.7712	pathogenic	-0.413	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
K/D	0.8252	likely_pathogenic	0.7785	pathogenic	0.029	Stabilizing	0.987	D	0.672	neutral	None	None	None	None	I
K/E	0.3674	ambiguous	0.3122	benign	0.082	Stabilizing	0.892	D	0.629	neutral	D	0.534443624	None	None	I
K/F	0.8625	likely_pathogenic	0.8372	pathogenic	-0.091	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
K/G	0.7078	likely_pathogenic	0.6503	pathogenic	-0.382	Destabilizing	0.975	D	0.628	neutral	None	None	None	None	I
K/H	0.3677	ambiguous	0.3351	benign	-0.587	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	I
K/I	0.6597	likely_pathogenic	0.5974	pathogenic	0.524	Stabilizing	0.983	D	0.709	prob.delet.	N	0.493165202	None	None	I
K/L	0.5095	ambiguous	0.4498	ambiguous	0.524	Stabilizing	0.975	D	0.628	neutral	None	None	None	None	I
K/M	0.3619	ambiguous	0.3118	benign	0.153	Stabilizing	0.999	D	0.64	neutral	None	None	None	None	I
K/N	0.6277	likely_pathogenic	0.5696	pathogenic	-0.129	Destabilizing	0.967	D	0.653	neutral	N	0.493213077	None	None	I
K/P	0.7502	likely_pathogenic	0.6804	pathogenic	0.341	Stabilizing	0.996	D	0.65	neutral	None	None	None	None	I
K/Q	0.2234	likely_benign	0.1938	benign	-0.213	Destabilizing	0.967	D	0.654	neutral	N	0.499349615	None	None	I
K/R	0.0871	likely_benign	0.085	benign	-0.262	Destabilizing	0.025	N	0.299	neutral	N	0.447440715	None	None	I
K/S	0.6599	likely_pathogenic	0.6086	pathogenic	-0.634	Destabilizing	0.916	D	0.655	neutral	None	None	None	None	I
K/T	0.3686	ambiguous	0.3164	benign	-0.409	Destabilizing	0.967	D	0.648	neutral	N	0.489264409	None	None	I
K/V	0.5858	likely_pathogenic	0.5226	ambiguous	0.341	Stabilizing	0.987	D	0.688	prob.neutral	None	None	None	None	I
K/W	0.8219	likely_pathogenic	0.7966	pathogenic	-0.087	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
K/Y	0.723	likely_pathogenic	0.6856	pathogenic	0.237	Stabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I

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.