TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23403	70432;70433;70434	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
N2AB	21762	65509;65510;65511	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
N2A	20835	62728;62729;62730	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
N2B	14338	43237;43238;43239	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
Novex-1	14463	43612;43613;43614	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
Novex-2	14530	43813;43814;43815	chr2:178575925;178575924;178575923	chr2:179440652;179440651;179440650
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: Ig-129
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.566
• 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	rs1399743496	-0.687	0.955	N	0.529	0.286	0.313818047136	gnomAD-4.0.0	1.59203E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86025E-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	0.1681	likely_benign	0.2053	benign	-1.21	Destabilizing	0.955	D	0.471	neutral	N	0.483860088	None	None	I
P/C	0.7884	likely_pathogenic	0.8595	pathogenic	-0.944	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
P/D	0.5654	likely_pathogenic	0.6497	pathogenic	-0.943	Destabilizing	0.995	D	0.557	neutral	None	None	None	None	I
P/E	0.4037	ambiguous	0.4838	ambiguous	-1.006	Destabilizing	0.995	D	0.552	neutral	None	None	None	None	I
P/F	0.8506	likely_pathogenic	0.9184	pathogenic	-1.14	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
P/G	0.3694	ambiguous	0.4445	ambiguous	-1.45	Destabilizing	0.995	D	0.547	neutral	None	None	None	None	I
P/H	0.3628	ambiguous	0.4616	ambiguous	-0.908	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	I
P/I	0.7649	likely_pathogenic	0.8476	pathogenic	-0.685	Destabilizing	0.995	D	0.67	neutral	None	None	None	None	I
P/K	0.5148	ambiguous	0.617	pathogenic	-0.929	Destabilizing	0.995	D	0.557	neutral	None	None	None	None	I
P/L	0.3204	likely_benign	0.4085	ambiguous	-0.685	Destabilizing	0.987	D	0.616	neutral	N	0.474683244	None	None	I
P/M	0.5891	likely_pathogenic	0.6842	pathogenic	-0.516	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	I
P/N	0.3849	ambiguous	0.4557	ambiguous	-0.67	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	I
P/Q	0.2852	likely_benign	0.3495	ambiguous	-0.937	Destabilizing	0.997	D	0.585	neutral	N	0.5105639	None	None	I
P/R	0.3915	ambiguous	0.4962	ambiguous	-0.339	Destabilizing	0.993	D	0.611	neutral	N	0.454595974	None	None	I
P/S	0.187	likely_benign	0.2212	benign	-1.163	Destabilizing	0.955	D	0.529	neutral	N	0.470256072	None	None	I
P/T	0.1901	likely_benign	0.2231	benign	-1.122	Destabilizing	0.362	N	0.342	neutral	N	0.475683322	None	None	I
P/V	0.5734	likely_pathogenic	0.68	pathogenic	-0.824	Destabilizing	0.99	D	0.557	neutral	None	None	None	None	I
P/W	0.8753	likely_pathogenic	0.9312	pathogenic	-1.212	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
P/Y	0.7564	likely_pathogenic	0.8513	pathogenic	-0.933	Destabilizing	1.0	D	0.651	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.