TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30619	92080;92081;92082	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
N2AB	28978	87157;87158;87159	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
N2A	28051	84376;84377;84378	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
N2B	21554	64885;64886;64887	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
Novex-1	21679	65260;65261;65262	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
Novex-2	21746	65461;65462;65463	chr2:178549867;178549866;178549865	chr2:179414594;179414593;179414592
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-111
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4688
• 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
T/I	rs1698630177	None	0.986	N	0.655	0.332	0.304435445954	gnomAD-4.0.0	3.54985E-06	None	None	None	None	I	None	0	3.15816E-05	None	0	0	None	0	0	0	1.73058E-05	0
T/K	None	None	0.986	N	0.567	0.387	0.281780670237	gnomAD-4.0.0	1.77493E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.73058E-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
T/A	0.093	likely_benign	0.1142	benign	-0.722	Destabilizing	0.058	N	0.155	neutral	N	0.455648327	None	None	I
T/C	0.3682	ambiguous	0.3893	ambiguous	-0.343	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
T/D	0.6862	likely_pathogenic	0.7623	pathogenic	0.086	Stabilizing	0.995	D	0.635	neutral	None	None	None	None	I
T/E	0.4677	ambiguous	0.579	pathogenic	0.009	Stabilizing	0.989	D	0.593	neutral	None	None	None	None	I
T/F	0.3152	likely_benign	0.4032	ambiguous	-1.253	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	I
T/G	0.3958	ambiguous	0.4126	ambiguous	-0.84	Destabilizing	0.929	D	0.574	neutral	None	None	None	None	I
T/H	0.3724	ambiguous	0.4314	ambiguous	-1.231	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
T/I	0.1236	likely_benign	0.176	benign	-0.521	Destabilizing	0.986	D	0.655	prob.neutral	N	0.448242352	None	None	I
T/K	0.2481	likely_benign	0.3306	benign	-0.381	Destabilizing	0.986	D	0.567	neutral	N	0.395234586	None	None	I
T/L	0.1121	likely_benign	0.1547	benign	-0.521	Destabilizing	0.963	D	0.565	neutral	None	None	None	None	I
T/M	0.0904	likely_benign	0.1172	benign	-0.056	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
T/N	0.192	likely_benign	0.2327	benign	-0.148	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	I
T/P	0.1922	likely_benign	0.229	benign	-0.562	Destabilizing	0.993	D	0.655	prob.neutral	N	0.436425061	None	None	I
T/Q	0.2949	likely_benign	0.3552	ambiguous	-0.479	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	I
T/R	0.2417	likely_benign	0.3052	benign	-0.097	Destabilizing	0.993	D	0.628	neutral	N	0.415417857	None	None	I
T/S	0.1304	likely_benign	0.152	benign	-0.423	Destabilizing	0.908	D	0.348	neutral	N	0.469868417	None	None	I
T/V	0.0963	likely_benign	0.1264	benign	-0.562	Destabilizing	0.929	D	0.435	neutral	None	None	None	None	I
T/W	0.8001	likely_pathogenic	0.8347	pathogenic	-1.155	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
T/Y	0.3743	ambiguous	0.4183	ambiguous	-0.902	Destabilizing	0.998	D	0.799	deleterious	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.