TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17453	52582;52583;52584	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
N2AB	15812	47659;47660;47661	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
N2A	14885	44878;44879;44880	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
N2B	8388	25387;25388;25389	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
Novex-1	8513	25762;25763;25764	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
Novex-2	8580	25963;25964;25965	chr2:178608654;178608653;178608652	chr2:179473381;179473380;179473379
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-14
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.598
• 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
P/S	None	None	0.521	N	0.515	0.084	0.215869574891	gnomAD-4.0.0	1.59554E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03177E-05

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	0.0709	likely_benign	0.0711	benign	-1.056	Destabilizing	0.003	N	0.321	neutral	N	0.448541501	None	None	I
P/C	0.4017	ambiguous	0.3896	ambiguous	-0.673	Destabilizing	0.02	N	0.517	neutral	None	None	None	None	I
P/D	0.6679	likely_pathogenic	0.6754	pathogenic	-1.096	Destabilizing	0.742	D	0.605	neutral	None	None	None	None	I
P/E	0.4095	ambiguous	0.404	ambiguous	-1.205	Destabilizing	0.742	D	0.581	neutral	None	None	None	None	I
P/F	0.5232	ambiguous	0.507	ambiguous	-1.203	Destabilizing	0.91	D	0.65	neutral	None	None	None	None	I
P/G	0.3872	ambiguous	0.387	ambiguous	-1.235	Destabilizing	0.59	D	0.576	neutral	None	None	None	None	I
P/H	0.3228	likely_benign	0.311	benign	-0.724	Destabilizing	0.02	N	0.485	neutral	None	None	None	None	I
P/I	0.2341	likely_benign	0.2328	benign	-0.709	Destabilizing	0.59	D	0.639	neutral	None	None	None	None	I
P/K	0.4433	ambiguous	0.4299	ambiguous	-0.754	Destabilizing	0.742	D	0.581	neutral	None	None	None	None	I
P/L	0.1381	likely_benign	0.1354	benign	-0.709	Destabilizing	0.007	N	0.496	neutral	N	0.4303211	None	None	I
P/M	0.2929	likely_benign	0.279	benign	-0.416	Destabilizing	0.91	D	0.643	neutral	None	None	None	None	I
P/N	0.479	ambiguous	0.4815	ambiguous	-0.425	Destabilizing	0.91	D	0.638	neutral	None	None	None	None	I
P/Q	0.2427	likely_benign	0.2318	benign	-0.784	Destabilizing	0.884	D	0.628	neutral	N	0.455006113	None	None	I
P/R	0.322	likely_benign	0.3165	benign	-0.103	Destabilizing	0.884	D	0.637	neutral	N	0.43397748	None	None	I
P/S	0.1619	likely_benign	0.1591	benign	-0.793	Destabilizing	0.521	D	0.515	neutral	N	0.465684467	None	None	I
P/T	0.1197	likely_benign	0.1237	benign	-0.815	Destabilizing	0.684	D	0.537	neutral	N	0.43695907	None	None	I
P/V	0.1584	likely_benign	0.1569	benign	-0.79	Destabilizing	0.59	D	0.579	neutral	None	None	None	None	I
P/W	0.7415	likely_pathogenic	0.7282	pathogenic	-1.231	Destabilizing	0.996	D	0.651	neutral	None	None	None	None	I
P/Y	0.5467	ambiguous	0.5468	ambiguous	-0.96	Destabilizing	0.835	D	0.655	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.