TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30410	91453;91454;91455	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
N2AB	28769	86530;86531;86532	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
N2A	27842	83749;83750;83751	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
N2B	21345	64258;64259;64260	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
Novex-1	21470	64633;64634;64635	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
Novex-2	21537	64834;64835;64836	chr2:178551672;178551671;178551670	chr2:179416399;179416398;179416397
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: Fn3-109
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2161
• 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/L	None	None	0.454	N	0.523	0.303	0.524792858863	gnomAD-4.0.0	1.61041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89884E-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	0.061	likely_benign	0.0654	benign	-1.556	Destabilizing	0.012	N	0.294	neutral	N	0.496564734	None	None	N
P/C	0.2962	likely_benign	0.3712	ambiguous	-0.953	Destabilizing	0.993	D	0.655	neutral	None	None	None	None	N
P/D	0.8321	likely_pathogenic	0.8771	pathogenic	-1.211	Destabilizing	0.974	D	0.499	neutral	None	None	None	None	N
P/E	0.5673	likely_pathogenic	0.6285	pathogenic	-1.217	Destabilizing	0.842	D	0.461	neutral	None	None	None	None	N
P/F	0.4104	ambiguous	0.5286	ambiguous	-1.264	Destabilizing	0.974	D	0.641	neutral	None	None	None	None	N
P/G	0.3675	ambiguous	0.4321	ambiguous	-1.858	Destabilizing	0.728	D	0.53	neutral	None	None	None	None	N
P/H	0.3222	likely_benign	0.3831	ambiguous	-1.327	Destabilizing	0.997	D	0.593	neutral	N	0.514009303	None	None	N
P/I	0.2718	likely_benign	0.3515	ambiguous	-0.826	Destabilizing	0.728	D	0.557	neutral	None	None	None	None	N
P/K	0.5498	ambiguous	0.6295	pathogenic	-1.072	Destabilizing	0.842	D	0.471	neutral	None	None	None	None	N
P/L	0.1591	likely_benign	0.2255	benign	-0.826	Destabilizing	0.454	N	0.523	neutral	N	0.495598651	None	None	N
P/M	0.2931	likely_benign	0.3746	ambiguous	-0.608	Destabilizing	0.974	D	0.591	neutral	None	None	None	None	N
P/N	0.5945	likely_pathogenic	0.6754	pathogenic	-0.857	Destabilizing	0.974	D	0.551	neutral	None	None	None	None	N
P/Q	0.2633	likely_benign	0.3099	benign	-1.06	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	N
P/R	0.3802	ambiguous	0.4615	ambiguous	-0.555	Destabilizing	0.966	D	0.554	neutral	N	0.496866099	None	None	N
P/S	0.1516	likely_benign	0.1778	benign	-1.415	Destabilizing	0.669	D	0.45	neutral	N	0.482774315	None	None	N
P/T	0.1616	likely_benign	0.1984	benign	-1.316	Destabilizing	0.801	D	0.466	neutral	N	0.501892529	None	None	N
P/V	0.165	likely_benign	0.2094	benign	-1.035	Destabilizing	0.007	N	0.446	neutral	None	None	None	None	N
P/W	0.6917	likely_pathogenic	0.7784	pathogenic	-1.409	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
P/Y	0.489	ambiguous	0.5945	pathogenic	-1.121	Destabilizing	0.991	D	0.642	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.