TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18940	57043;57044;57045	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
N2AB	17299	52120;52121;52122	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
N2A	16372	49339;49340;49341	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
N2B	9875	29848;29849;29850	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
Novex-1	10000	30223;30224;30225	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
Novex-2	10067	30424;30425;30426	chr2:178598892;178598891;178598890	chr2:179463619;179463618;179463617
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: Fn3-25
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.8332
• 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/E	None	None	0.722	N	0.603	0.132	0.186928172975	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/N	None	None	0.722	N	0.597	0.135	0.112648838833	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.4703	ambiguous	0.5743	pathogenic	0.06	Stabilizing	0.775	D	0.617	neutral	None	None	None	None	I
K/C	0.7662	likely_pathogenic	0.8515	pathogenic	-0.322	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	I
K/D	0.7736	likely_pathogenic	0.7989	pathogenic	-0.037	Destabilizing	0.923	D	0.628	neutral	None	None	None	None	I
K/E	0.3331	likely_benign	0.4045	ambiguous	-0.024	Destabilizing	0.722	D	0.603	neutral	N	0.441362025	None	None	I
K/F	0.8708	likely_pathogenic	0.913	pathogenic	-0.149	Destabilizing	0.987	D	0.696	prob.neutral	None	None	None	None	I
K/G	0.5846	likely_pathogenic	0.6804	pathogenic	-0.125	Destabilizing	0.775	D	0.611	neutral	None	None	None	None	I
K/H	0.3649	ambiguous	0.4393	ambiguous	-0.274	Destabilizing	0.961	D	0.665	neutral	None	None	None	None	I
K/I	0.5898	likely_pathogenic	0.6521	pathogenic	0.471	Stabilizing	0.949	D	0.707	prob.neutral	N	0.467257761	None	None	I
K/L	0.5085	ambiguous	0.6093	pathogenic	0.471	Stabilizing	0.775	D	0.611	neutral	None	None	None	None	I
K/M	0.4512	ambiguous	0.5363	ambiguous	0.065	Stabilizing	0.996	D	0.66	neutral	None	None	None	None	I
K/N	0.6316	likely_pathogenic	0.6944	pathogenic	0.117	Stabilizing	0.722	D	0.597	neutral	N	0.453003171	None	None	I
K/P	0.5047	ambiguous	0.5868	pathogenic	0.361	Stabilizing	0.987	D	0.669	neutral	None	None	None	None	I
K/Q	0.1715	likely_benign	0.2109	benign	None	Stabilizing	0.722	D	0.615	neutral	N	0.442863535	None	None	I
K/R	0.076	likely_benign	0.0887	benign	-0.038	Destabilizing	0.003	N	0.17	neutral	N	0.393570866	None	None	I
K/S	0.5757	likely_pathogenic	0.6667	pathogenic	-0.304	Destabilizing	0.775	D	0.575	neutral	None	None	None	None	I
K/T	0.2886	likely_benign	0.3595	ambiguous	-0.148	Destabilizing	0.722	D	0.61	neutral	N	0.394704229	None	None	I
K/V	0.5094	ambiguous	0.5687	pathogenic	0.361	Stabilizing	0.961	D	0.633	neutral	None	None	None	None	I
K/W	0.8061	likely_pathogenic	0.886	pathogenic	-0.221	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	I
K/Y	0.7675	likely_pathogenic	0.8054	pathogenic	0.137	Stabilizing	0.987	D	0.698	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.