TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22840	68743;68744;68745	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
N2AB	21199	63820;63821;63822	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
N2A	20272	61039;61040;61041	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
N2B	13775	41548;41549;41550	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
Novex-1	13900	41923;41924;41925	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
Novex-2	13967	42124;42125;42126	chr2:178577997;178577996;178577995	chr2:179442724;179442723;179442722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-53
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.8799
• 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
D/E	None	None	0.999	N	0.431	0.213	0.330069100803	gnomAD-4.0.0	1.59428E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43831E-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
D/A	0.8064	likely_pathogenic	0.8311	pathogenic	-0.548	Destabilizing	1.0	D	0.743	deleterious	N	0.505176723	None	None	I
D/C	0.9782	likely_pathogenic	0.9829	pathogenic	-0.299	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
D/E	0.8654	likely_pathogenic	0.8486	pathogenic	-0.528	Destabilizing	0.999	D	0.431	neutral	N	0.512006694	None	None	I
D/F	0.965	likely_pathogenic	0.9687	pathogenic	-0.349	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
D/G	0.9065	likely_pathogenic	0.9183	pathogenic	-0.801	Destabilizing	1.0	D	0.793	deleterious	N	0.519954174	None	None	I
D/H	0.8835	likely_pathogenic	0.9154	pathogenic	-0.393	Destabilizing	1.0	D	0.888	deleterious	N	0.50385949	None	None	I
D/I	0.9651	likely_pathogenic	0.9622	pathogenic	0.092	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
D/K	0.9779	likely_pathogenic	0.981	pathogenic	-0.413	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
D/L	0.904	likely_pathogenic	0.9074	pathogenic	0.092	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
D/M	0.981	likely_pathogenic	0.98	pathogenic	0.316	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
D/N	0.5344	ambiguous	0.5839	pathogenic	-0.625	Destabilizing	1.0	D	0.791	deleterious	N	0.480386411	None	None	I
D/P	0.9796	likely_pathogenic	0.9791	pathogenic	-0.098	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
D/Q	0.9518	likely_pathogenic	0.9553	pathogenic	-0.556	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
D/R	0.9759	likely_pathogenic	0.9796	pathogenic	-0.136	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
D/S	0.5869	likely_pathogenic	0.6371	pathogenic	-0.805	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
D/T	0.9109	likely_pathogenic	0.9183	pathogenic	-0.619	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
D/V	0.9135	likely_pathogenic	0.9116	pathogenic	-0.098	Destabilizing	1.0	D	0.785	deleterious	N	0.495110078	None	None	I
D/W	0.9917	likely_pathogenic	0.9931	pathogenic	-0.203	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
D/Y	0.7935	likely_pathogenic	0.8314	pathogenic	-0.151	Destabilizing	1.0	D	0.813	deleterious	N	0.512506771	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.