TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6714	20365;20366;20367	chr2:178727225;178727224;178727223	chr2:179591952;179591951;179591950
N2AB	6397	19414;19415;19416	chr2:178727225;178727224;178727223	chr2:179591952;179591951;179591950
N2A	5470	16633;16634;16635	chr2:178727225;178727224;178727223	chr2:179591952;179591951;179591950
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-51
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.2282
• 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
Y/C	rs774722320	-1.631	0.003	N	0.423	0.44	0.493695379898	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
Y/C	rs774722320	-1.631	0.003	N	0.423	0.44	0.493695379898	gnomAD-4.0.0	2.05329E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6991E-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
Y/A	0.6567	likely_pathogenic	0.7045	pathogenic	-2.955	Highly Destabilizing	0.388	N	0.495	neutral	None	None	None	None	N
Y/C	0.1997	likely_benign	0.2054	benign	-1.944	Destabilizing	0.003	N	0.423	neutral	N	0.514107068	None	None	N
Y/D	0.6219	likely_pathogenic	0.716	pathogenic	-2.667	Highly Destabilizing	0.912	D	0.601	neutral	D	0.537491242	None	None	N
Y/E	0.7592	likely_pathogenic	0.8177	pathogenic	-2.514	Highly Destabilizing	0.818	D	0.559	neutral	None	None	None	None	N
Y/F	0.1083	likely_benign	0.0965	benign	-1.247	Destabilizing	0.001	N	0.171	neutral	N	0.475358035	None	None	N
Y/G	0.6226	likely_pathogenic	0.7147	pathogenic	-3.363	Highly Destabilizing	0.818	D	0.577	neutral	None	None	None	None	N
Y/H	0.2219	likely_benign	0.2515	benign	-1.925	Destabilizing	0.912	D	0.527	neutral	N	0.51239627	None	None	N
Y/I	0.3568	ambiguous	0.382	ambiguous	-1.641	Destabilizing	0.241	N	0.497	neutral	None	None	None	None	N
Y/K	0.7476	likely_pathogenic	0.8262	pathogenic	-2.08	Highly Destabilizing	0.818	D	0.557	neutral	None	None	None	None	N
Y/L	0.395	ambiguous	0.4303	ambiguous	-1.641	Destabilizing	0.002	N	0.289	neutral	None	None	None	None	N
Y/M	0.5709	likely_pathogenic	0.5963	pathogenic	-1.376	Destabilizing	0.69	D	0.538	neutral	None	None	None	None	N
Y/N	0.2868	likely_benign	0.3547	ambiguous	-2.66	Highly Destabilizing	0.912	D	0.575	neutral	N	0.507777192	None	None	N
Y/P	0.9476	likely_pathogenic	0.9686	pathogenic	-2.087	Highly Destabilizing	0.932	D	0.599	neutral	None	None	None	None	N
Y/Q	0.5665	likely_pathogenic	0.6475	pathogenic	-2.48	Highly Destabilizing	0.932	D	0.555	neutral	None	None	None	None	N
Y/R	0.5937	likely_pathogenic	0.6894	pathogenic	-1.722	Destabilizing	0.818	D	0.575	neutral	None	None	None	None	N
Y/S	0.4021	ambiguous	0.4719	ambiguous	-3.128	Highly Destabilizing	0.773	D	0.538	neutral	N	0.491874983	None	None	N
Y/T	0.5328	ambiguous	0.6068	pathogenic	-2.854	Highly Destabilizing	0.818	D	0.539	neutral	None	None	None	None	N
Y/V	0.3228	likely_benign	0.3382	benign	-2.087	Highly Destabilizing	0.241	N	0.488	neutral	None	None	None	None	N
Y/W	0.46	ambiguous	0.4795	ambiguous	-0.735	Destabilizing	0.944	D	0.513	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.