TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9038	27337;27338;27339	chr2:178712913;178712912;178712911	chr2:179577640;179577639;179577638
N2AB	8721	26386;26387;26388	chr2:178712913;178712912;178712911	chr2:179577640;179577639;179577638
N2A	7794	23605;23606;23607	chr2:178712913;178712912;178712911	chr2:179577640;179577639;179577638
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-76
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0882
• 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
F/V	None	None	0.248	D	0.559	0.687	0.79156486764	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
F/A	0.967	likely_pathogenic	0.982	pathogenic	-2.192	Highly Destabilizing	0.97	D	0.79	deleterious	None	None	None	None	N
F/C	0.869	likely_pathogenic	0.9113	pathogenic	-1.391	Destabilizing	1.0	D	0.881	deleterious	D	0.62866573	None	None	N
F/D	0.9985	likely_pathogenic	0.9994	pathogenic	-3.174	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
F/E	0.9973	likely_pathogenic	0.9989	pathogenic	-2.914	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
F/G	0.9912	likely_pathogenic	0.9954	pathogenic	-2.674	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
F/H	0.9823	likely_pathogenic	0.9906	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
F/I	0.5043	ambiguous	0.6097	pathogenic	-0.604	Destabilizing	0.925	D	0.667	neutral	D	0.541034027	None	None	N
F/K	0.9968	likely_pathogenic	0.9987	pathogenic	-1.869	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
F/L	0.8439	likely_pathogenic	0.861	pathogenic	-0.604	Destabilizing	0.071	N	0.333	neutral	N	0.451633026	None	None	N
F/M	0.7221	likely_pathogenic	0.7769	pathogenic	-0.546	Destabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	N
F/N	0.9928	likely_pathogenic	0.9964	pathogenic	-2.603	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9998	pathogenic	-1.149	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
F/Q	0.994	likely_pathogenic	0.9973	pathogenic	-2.307	Highly Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
F/R	0.991	likely_pathogenic	0.9958	pathogenic	-1.963	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
F/S	0.9763	likely_pathogenic	0.9897	pathogenic	-3.02	Highly Destabilizing	0.994	D	0.837	deleterious	D	0.62866573	None	None	N
F/T	0.983	likely_pathogenic	0.9918	pathogenic	-2.622	Highly Destabilizing	0.97	D	0.823	deleterious	None	None	None	None	N
F/V	0.5593	ambiguous	0.6535	pathogenic	-1.149	Destabilizing	0.248	N	0.559	neutral	D	0.52352586	None	None	N
F/W	0.8765	likely_pathogenic	0.9143	pathogenic	-0.133	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
F/Y	0.5709	likely_pathogenic	0.6095	pathogenic	-0.53	Destabilizing	0.993	D	0.637	neutral	D	0.580173678	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.