TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30722	92389;92390;92391	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
N2AB	29081	87466;87467;87468	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
N2A	28154	84685;84686;84687	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
N2B	21657	65194;65195;65196	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
Novex-1	21782	65569;65570;65571	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
Novex-2	21849	65770;65771;65772	chr2:178549462;178549461;178549460	chr2:179414189;179414188;179414187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-112
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2512
• 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/V	rs2154148189	None	0.928	N	0.797	0.354	0.533179623451	gnomAD-4.0.0	6.88776E-07	None	None	None	None	N	None	3.0259E-05	0	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	0.4849	ambiguous	0.4692	ambiguous	-1.165	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
A/D	0.5795	likely_pathogenic	0.5993	pathogenic	-1.887	Destabilizing	0.978	D	0.9	deleterious	D	0.532147373	None	None	N
A/E	0.3268	likely_benign	0.3396	benign	-1.965	Destabilizing	0.983	D	0.859	deleterious	None	None	None	None	N
A/F	0.4668	ambiguous	0.4936	ambiguous	-1.343	Destabilizing	0.992	D	0.912	deleterious	None	None	None	None	N
A/G	0.2068	likely_benign	0.2157	benign	-1.144	Destabilizing	0.865	D	0.737	prob.delet.	D	0.532400862	None	None	N
A/H	0.5661	likely_pathogenic	0.571	pathogenic	-1.1	Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	N
A/I	0.3457	ambiguous	0.3531	ambiguous	-0.67	Destabilizing	0.992	D	0.869	deleterious	None	None	None	None	N
A/K	0.4472	ambiguous	0.4475	ambiguous	-1.148	Destabilizing	0.968	D	0.855	deleterious	None	None	None	None	N
A/L	0.3126	likely_benign	0.3144	benign	-0.67	Destabilizing	0.944	D	0.83	deleterious	None	None	None	None	N
A/M	0.3005	likely_benign	0.3032	benign	-0.54	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
A/N	0.4632	ambiguous	0.4757	ambiguous	-0.981	Destabilizing	0.968	D	0.903	deleterious	None	None	None	None	N
A/P	0.1933	likely_benign	0.2124	benign	-0.736	Destabilizing	0.989	D	0.868	deleterious	N	0.403140072	None	None	N
A/Q	0.342	ambiguous	0.3368	benign	-1.307	Destabilizing	0.983	D	0.859	deleterious	None	None	None	None	N
A/R	0.3914	ambiguous	0.3924	ambiguous	-0.658	Destabilizing	0.983	D	0.863	deleterious	None	None	None	None	N
A/S	0.1183	likely_benign	0.1157	benign	-1.202	Destabilizing	0.284	N	0.48	neutral	N	0.481251195	None	None	N
A/T	0.1322	likely_benign	0.1338	benign	-1.213	Destabilizing	0.865	D	0.745	deleterious	N	0.514043118	None	None	N
A/V	0.185	likely_benign	0.1687	benign	-0.736	Destabilizing	0.928	D	0.797	deleterious	N	0.478492944	None	None	N
A/W	0.8653	likely_pathogenic	0.8758	pathogenic	-1.543	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
A/Y	0.5974	likely_pathogenic	0.6068	pathogenic	-1.178	Destabilizing	0.999	D	0.91	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.