TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15595	47008;47009;47010	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
N2AB	13954	42085;42086;42087	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
N2A	13027	39304;39305;39306	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
N2B	6530	19813;19814;19815	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
Novex-1	6655	20188;20189;20190	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
Novex-2	6722	20389;20390;20391	chr2:178618767;178618766;178618765	chr2:179483494;179483493;179483492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-108
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.2933
• 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/R	None	None	1.0	D	0.817	0.635	0.622259118589	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
P/S	None	None	1.0	D	0.781	0.621	0.543647257999	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8475	likely_pathogenic	0.9023	pathogenic	-1.158	Destabilizing	1.0	D	0.747	deleterious	D	0.562488489	None	None	I
P/C	0.9836	likely_pathogenic	0.9925	pathogenic	-0.478	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/D	0.9765	likely_pathogenic	0.9853	pathogenic	-1.154	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
P/E	0.9356	likely_pathogenic	0.9513	pathogenic	-1.195	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/F	0.9906	likely_pathogenic	0.9949	pathogenic	-1.063	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
P/G	0.9291	likely_pathogenic	0.9459	pathogenic	-1.405	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/H	0.953	likely_pathogenic	0.9758	pathogenic	-1.071	Destabilizing	1.0	D	0.788	deleterious	D	0.579297634	None	None	I
P/I	0.9508	likely_pathogenic	0.9698	pathogenic	-0.597	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/K	0.9612	likely_pathogenic	0.9726	pathogenic	-1.004	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
P/L	0.8785	likely_pathogenic	0.9257	pathogenic	-0.597	Destabilizing	1.0	D	0.791	deleterious	D	0.579297634	None	None	I
P/M	0.9669	likely_pathogenic	0.9835	pathogenic	-0.387	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/N	0.9749	likely_pathogenic	0.9821	pathogenic	-0.633	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/Q	0.9084	likely_pathogenic	0.9419	pathogenic	-0.839	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/R	0.9148	likely_pathogenic	0.9408	pathogenic	-0.476	Destabilizing	1.0	D	0.817	deleterious	D	0.563121173	None	None	I
P/S	0.923	likely_pathogenic	0.9516	pathogenic	-0.986	Destabilizing	1.0	D	0.781	deleterious	D	0.561165802	None	None	I
P/T	0.8593	likely_pathogenic	0.9105	pathogenic	-0.933	Destabilizing	1.0	D	0.775	deleterious	D	0.563121173	None	None	I
P/V	0.9015	likely_pathogenic	0.9359	pathogenic	-0.751	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/W	0.9928	likely_pathogenic	0.9969	pathogenic	-1.252	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/Y	0.9864	likely_pathogenic	0.9923	pathogenic	-0.967	Destabilizing	1.0	D	0.826	deleterious	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.