TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30452	91579;91580;91581	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
N2AB	28811	86656;86657;86658	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
N2A	27884	83875;83876;83877	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
N2B	21387	64384;64385;64386	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
Novex-1	21512	64759;64760;64761	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
Novex-2	21579	64960;64961;64962	chr2:178551177;178551176;178551175	chr2:179415904;179415903;179415902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-110
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3147
• 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
S/N	None	None	0.99	N	0.705	0.312	0.32714864917	gnomAD-4.0.0	1.59175E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-05	None	0	0	0	0	0
S/R	None	None	0.99	N	0.638	0.41	0.331365685468	gnomAD-4.0.0	2.73722E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59824E-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
S/A	0.1733	likely_benign	0.1687	benign	-0.595	Destabilizing	0.559	D	0.58	neutral	None	None	None	None	I
S/C	0.1399	likely_benign	0.1163	benign	-0.357	Destabilizing	0.032	N	0.58	neutral	N	0.488502442	None	None	I
S/D	0.9559	likely_pathogenic	0.9482	pathogenic	-0.102	Destabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	I
S/E	0.9512	likely_pathogenic	0.9457	pathogenic	-0.188	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	I
S/F	0.4983	ambiguous	0.5071	ambiguous	-1.177	Destabilizing	0.978	D	0.723	prob.delet.	None	None	None	None	I
S/G	0.3128	likely_benign	0.2939	benign	-0.715	Destabilizing	0.822	D	0.614	neutral	N	0.468678851	None	None	I
S/H	0.6922	likely_pathogenic	0.678	pathogenic	-1.269	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	I
S/I	0.6692	likely_pathogenic	0.646	pathogenic	-0.402	Destabilizing	0.942	D	0.725	prob.delet.	N	0.513733041	None	None	I
S/K	0.9772	likely_pathogenic	0.9755	pathogenic	-0.545	Destabilizing	0.978	D	0.701	prob.neutral	None	None	None	None	I
S/L	0.3492	ambiguous	0.3438	ambiguous	-0.402	Destabilizing	0.754	D	0.687	prob.neutral	None	None	None	None	I
S/M	0.4526	ambiguous	0.4415	ambiguous	0.059	Stabilizing	0.998	D	0.632	neutral	None	None	None	None	I
S/N	0.6019	likely_pathogenic	0.5757	pathogenic	-0.327	Destabilizing	0.99	D	0.705	prob.neutral	N	0.496780875	None	None	I
S/P	0.9823	likely_pathogenic	0.9774	pathogenic	-0.438	Destabilizing	0.993	D	0.641	neutral	None	None	None	None	I
S/Q	0.8424	likely_pathogenic	0.8313	pathogenic	-0.649	Destabilizing	0.993	D	0.679	prob.neutral	None	None	None	None	I
S/R	0.955	likely_pathogenic	0.9529	pathogenic	-0.304	Destabilizing	0.99	D	0.638	neutral	N	0.490638355	None	None	I
S/T	0.3533	ambiguous	0.3409	ambiguous	-0.448	Destabilizing	0.822	D	0.639	neutral	N	0.484018991	None	None	I
S/V	0.5613	ambiguous	0.5395	ambiguous	-0.438	Destabilizing	0.915	D	0.69	prob.neutral	None	None	None	None	I
S/W	0.6682	likely_pathogenic	0.6453	pathogenic	-1.122	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
S/Y	0.4707	ambiguous	0.4522	ambiguous	-0.863	Destabilizing	0.993	D	0.717	prob.delet.	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.