TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22240	66943;66944;66945	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
N2AB	20599	62020;62021;62022	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
N2A	19672	59239;59240;59241	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
N2B	13175	39748;39749;39750	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
Novex-1	13300	40123;40124;40125	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
Novex-2	13367	40324;40325;40326	chr2:178581550;178581549;178581548	chr2:179446277;179446276;179446275
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: Fn3-49
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.675
• Predicted PPI site: I

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	rs745376985	-0.537	0.994	N	0.621	0.341	0.381916209588	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
Y/C	rs745376985	-0.537	0.994	N	0.621	0.341	0.381916209588	gnomAD-4.0.0	1.37016E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16066E-05	1.65959E-05
Y/N	None	None	0.884	N	0.627	0.334	0.500678981321	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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	0.6486	likely_pathogenic	0.617	pathogenic	-1.444	Destabilizing	0.543	D	0.565	neutral	None	None	None	None	I
Y/C	0.2007	likely_benign	0.1911	benign	-0.802	Destabilizing	0.994	D	0.621	neutral	N	0.439092511	None	None	I
Y/D	0.592	likely_pathogenic	0.5648	pathogenic	0.689	Stabilizing	0.884	D	0.624	neutral	N	0.398862042	None	None	I
Y/E	0.7857	likely_pathogenic	0.7506	pathogenic	0.77	Stabilizing	0.742	D	0.629	neutral	None	None	None	None	I
Y/F	0.1036	likely_benign	0.1006	benign	-0.394	Destabilizing	0.003	N	0.261	neutral	N	0.385124741	None	None	I
Y/G	0.7134	likely_pathogenic	0.6852	pathogenic	-1.716	Destabilizing	0.742	D	0.615	neutral	None	None	None	None	I
Y/H	0.3441	ambiguous	0.3142	benign	-0.148	Destabilizing	0.015	N	0.289	neutral	N	0.429184949	None	None	I
Y/I	0.4746	ambiguous	0.4476	ambiguous	-0.66	Destabilizing	0.59	D	0.549	neutral	None	None	None	None	I
Y/K	0.7066	likely_pathogenic	0.659	pathogenic	-0.614	Destabilizing	0.91	D	0.625	neutral	None	None	None	None	I
Y/L	0.5072	ambiguous	0.464	ambiguous	-0.66	Destabilizing	0.373	N	0.538	neutral	None	None	None	None	I
Y/M	0.6359	likely_pathogenic	0.6018	pathogenic	-0.687	Destabilizing	0.953	D	0.618	neutral	None	None	None	None	I
Y/N	0.3709	ambiguous	0.3185	benign	-1.019	Destabilizing	0.884	D	0.627	neutral	N	0.43926587	None	None	I
Y/P	0.7546	likely_pathogenic	0.736	pathogenic	-0.911	Destabilizing	0.984	D	0.625	neutral	None	None	None	None	I
Y/Q	0.6728	likely_pathogenic	0.6137	pathogenic	-0.808	Destabilizing	0.91	D	0.623	neutral	None	None	None	None	I
Y/R	0.6141	likely_pathogenic	0.5636	ambiguous	-0.382	Destabilizing	0.91	D	0.645	neutral	None	None	None	None	I
Y/S	0.4285	ambiguous	0.3875	ambiguous	-1.646	Destabilizing	0.684	D	0.627	neutral	N	0.399150044	None	None	I
Y/T	0.5994	likely_pathogenic	0.5634	ambiguous	-1.467	Destabilizing	0.742	D	0.627	neutral	None	None	None	None	I
Y/V	0.3918	ambiguous	0.374	ambiguous	-0.911	Destabilizing	0.037	N	0.374	neutral	None	None	None	None	I
Y/W	0.5088	ambiguous	0.5021	ambiguous	-0.125	Destabilizing	0.984	D	0.623	neutral	None	None	None	None	I

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.