TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3034	9325;9326;9327	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
N2AB	3034	9325;9326;9327	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
N2A	3034	9325;9326;9327	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
N2B	2988	9187;9188;9189	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
Novex-1	2988	9187;9188;9189	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
Novex-2	2988	9187;9188;9189	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461
Novex-3	3034	9325;9326;9327	chr2:178768736;178768735;178768734	chr2:179633463;179633462;179633461

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-20
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.1029
• 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
D/V	None	None	0.994	D	0.883	0.874	0.843089832369	gnomAD-4.0.0	3.18129E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.7635E-05	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
D/A	0.9894	likely_pathogenic	0.9827	pathogenic	0.225	Stabilizing	0.919	D	0.784	deleterious	D	0.72974757	None	None	N
D/C	0.9977	likely_pathogenic	0.9969	pathogenic	0.067	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
D/E	0.9627	likely_pathogenic	0.9417	pathogenic	-0.861	Destabilizing	0.979	D	0.605	neutral	D	0.730805165	None	None	N
D/F	0.9951	likely_pathogenic	0.9919	pathogenic	0.851	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
D/G	0.9936	likely_pathogenic	0.988	pathogenic	-0.226	Destabilizing	0.067	N	0.479	neutral	D	0.729006433	None	None	N
D/H	0.9858	likely_pathogenic	0.98	pathogenic	0.383	Stabilizing	0.999	D	0.813	deleterious	D	0.623681428	None	None	N
D/I	0.9969	likely_pathogenic	0.9951	pathogenic	1.437	Stabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
D/K	0.9968	likely_pathogenic	0.9952	pathogenic	-0.353	Destabilizing	0.991	D	0.83	deleterious	None	None	None	None	N
D/L	0.9929	likely_pathogenic	0.9899	pathogenic	1.437	Stabilizing	0.995	D	0.881	deleterious	None	None	None	None	N
D/M	0.9965	likely_pathogenic	0.9948	pathogenic	1.823	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
D/N	0.9296	likely_pathogenic	0.8929	pathogenic	-1.019	Destabilizing	0.988	D	0.752	deleterious	D	0.693665427	None	None	N
D/P	0.9996	likely_pathogenic	0.9995	pathogenic	1.063	Stabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
D/Q	0.994	likely_pathogenic	0.9898	pathogenic	-0.683	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
D/R	0.9977	likely_pathogenic	0.9961	pathogenic	-0.265	Destabilizing	0.995	D	0.866	deleterious	None	None	None	None	N
D/S	0.979	likely_pathogenic	0.9609	pathogenic	-1.275	Destabilizing	0.968	D	0.649	neutral	None	None	None	None	N
D/T	0.9957	likely_pathogenic	0.9929	pathogenic	-0.88	Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
D/V	0.9893	likely_pathogenic	0.9842	pathogenic	1.063	Stabilizing	0.994	D	0.883	deleterious	D	0.729007926	None	None	N
D/W	0.9993	likely_pathogenic	0.9988	pathogenic	0.826	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/Y	0.971	likely_pathogenic	0.9507	pathogenic	1.047	Stabilizing	0.999	D	0.885	deleterious	D	0.729087228	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.