TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9989	30190;30191;30192	chr2:178704405;178704404;178704403	chr2:179569132;179569131;179569130
N2AB	9672	29239;29240;29241	chr2:178704405;178704404;178704403	chr2:179569132;179569131;179569130
N2A	8745	26458;26459;26460	chr2:178704405;178704404;178704403	chr2:179569132;179569131;179569130
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-85
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1593
• 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
P/T	rs1553877891	None	0.98	None	0.525	0.646	0.780941640523	gnomAD-4.0.0	8.21707E-06	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	1.7343E-04	9.00135E-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
P/A	0.252	likely_benign	0.2929	benign	-0.604	Destabilizing	0.961	D	0.513	neutral	None	None	None	None	N
P/C	0.9656	likely_pathogenic	0.9726	pathogenic	-0.96	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
P/D	0.9505	likely_pathogenic	0.9429	pathogenic	-0.429	Destabilizing	0.996	D	0.539	neutral	None	None	None	None	N
P/E	0.8572	likely_pathogenic	0.8499	pathogenic	-0.478	Destabilizing	0.97	D	0.524	neutral	None	None	None	None	N
P/F	0.9732	likely_pathogenic	0.9775	pathogenic	-0.665	Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
P/G	0.8448	likely_pathogenic	0.8568	pathogenic	-0.742	Destabilizing	0.985	D	0.507	neutral	None	None	None	None	N
P/H	0.8316	likely_pathogenic	0.8365	pathogenic	-0.055	Destabilizing	0.151	N	0.407	neutral	None	None	None	None	N
P/I	0.8813	likely_pathogenic	0.8963	pathogenic	-0.347	Destabilizing	0.983	D	0.571	neutral	None	None	None	None	N
P/K	0.8684	likely_pathogenic	0.8627	pathogenic	-0.542	Destabilizing	0.991	D	0.527	neutral	None	None	None	None	N
P/L	0.5445	ambiguous	0.5681	pathogenic	-0.347	Destabilizing	0.071	N	0.427	neutral	None	None	None	None	N
P/M	0.8819	likely_pathogenic	0.8928	pathogenic	-0.776	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	N
P/N	0.922	likely_pathogenic	0.9216	pathogenic	-0.524	Destabilizing	0.991	D	0.564	neutral	None	None	None	None	N
P/Q	0.7816	likely_pathogenic	0.7912	pathogenic	-0.637	Destabilizing	0.996	D	0.572	neutral	None	None	None	None	N
P/R	0.756	likely_pathogenic	0.7614	pathogenic	-0.123	Destabilizing	0.989	D	0.569	neutral	None	None	None	None	N
P/S	0.65	likely_pathogenic	0.6717	pathogenic	-0.885	Destabilizing	0.961	D	0.514	neutral	None	None	None	None	N
P/T	0.5462	ambiguous	0.5714	pathogenic	-0.825	Destabilizing	0.98	D	0.525	neutral	None	None	None	None	N
P/V	0.7297	likely_pathogenic	0.764	pathogenic	-0.405	Destabilizing	0.942	D	0.524	neutral	None	None	None	None	N
P/W	0.9859	likely_pathogenic	0.9876	pathogenic	-0.727	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
P/Y	0.9532	likely_pathogenic	0.9594	pathogenic	-0.467	Destabilizing	0.991	D	0.605	neutral	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.