TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3256	9991;9992;9993	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
N2AB	3256	9991;9992;9993	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
N2A	3256	9991;9992;9993	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
N2B	3210	9853;9854;9855	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
Novex-1	3210	9853;9854;9855	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
Novex-2	3210	9853;9854;9855	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474
Novex-3	3256	9991;9992;9993	chr2:178764749;178764748;178764747	chr2:179629476;179629475;179629474

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-23
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1235
• Predicted PPI site: N

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
A/T	rs1322989995	-1.198	1.0	D	0.723	0.548	0.360565625551	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
A/T	rs1322989995	-1.198	1.0	D	0.723	0.548	0.360565625551	gnomAD-4.0.0	1.59087E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	0	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
A/C	0.7701	likely_pathogenic	0.8506	pathogenic	-0.64	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/D	0.992	likely_pathogenic	0.9976	pathogenic	-1.686	Destabilizing	1.0	D	0.879	deleterious	D	0.708624963	None	None	N
A/E	0.9781	likely_pathogenic	0.9916	pathogenic	-1.504	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
A/F	0.9196	likely_pathogenic	0.9636	pathogenic	-0.519	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
A/G	0.4589	ambiguous	0.592	pathogenic	-1.262	Destabilizing	1.0	D	0.6	neutral	D	0.669303304	None	None	N
A/H	0.9885	likely_pathogenic	0.9956	pathogenic	-1.749	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
A/I	0.6662	likely_pathogenic	0.8054	pathogenic	0.446	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/K	0.9926	likely_pathogenic	0.9974	pathogenic	-1.044	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/L	0.6327	likely_pathogenic	0.7711	pathogenic	0.446	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
A/M	0.746	likely_pathogenic	0.8792	pathogenic	0.322	Stabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
A/N	0.9764	likely_pathogenic	0.9918	pathogenic	-1.209	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
A/P	0.9874	likely_pathogenic	0.9943	pathogenic	0.08	Stabilizing	1.0	D	0.885	deleterious	D	0.686245778	None	None	N
A/Q	0.9614	likely_pathogenic	0.982	pathogenic	-1.024	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
A/R	0.9764	likely_pathogenic	0.9898	pathogenic	-1.162	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
A/S	0.2836	likely_benign	0.398	ambiguous	-1.641	Destabilizing	1.0	D	0.607	neutral	D	0.668792952	None	None	N
A/T	0.3218	likely_benign	0.5286	ambiguous	-1.325	Destabilizing	1.0	D	0.723	prob.delet.	D	0.577713214	None	None	N
A/V	0.2964	likely_benign	0.4298	ambiguous	0.08	Stabilizing	1.0	D	0.631	neutral	N	0.459597053	None	None	N
A/W	0.9952	likely_pathogenic	0.9985	pathogenic	-1.295	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/Y	0.9816	likely_pathogenic	0.9929	pathogenic	-0.661	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N

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.