TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13864	41815;41816;41817	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
N2AB	12223	36892;36893;36894	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
N2A	11296	34111;34112;34113	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
N2B	4799	14620;14621;14622	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
Novex-1	4924	14995;14996;14997	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
Novex-2	4991	15196;15197;15198	chr2:178635981;178635980;178635979	chr2:179500708;179500707;179500706
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-88
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.7296
• 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
S/P	None	None	0.988	N	0.466	0.244	0.199424873507	gnomAD-4.0.0	1.37961E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81135E-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
S/A	0.1452	likely_benign	0.1733	benign	-0.959	Destabilizing	0.061	N	0.093	neutral	N	0.332852067	None	None	N
S/C	0.2999	likely_benign	0.3022	benign	-0.717	Destabilizing	0.999	D	0.383	neutral	N	0.343570829	None	None	N
S/D	0.992	likely_pathogenic	0.9917	pathogenic	-0.475	Destabilizing	0.969	D	0.405	neutral	None	None	None	None	N
S/E	0.9947	likely_pathogenic	0.9943	pathogenic	-0.379	Destabilizing	0.969	D	0.321	neutral	None	None	None	None	N
S/F	0.9718	likely_pathogenic	0.9788	pathogenic	-1.056	Destabilizing	0.996	D	0.547	neutral	N	0.338716975	None	None	N
S/G	0.3839	ambiguous	0.4118	ambiguous	-1.28	Destabilizing	0.759	D	0.376	neutral	None	None	None	None	N
S/H	0.9838	likely_pathogenic	0.9836	pathogenic	-1.659	Destabilizing	0.999	D	0.383	neutral	None	None	None	None	N
S/I	0.9257	likely_pathogenic	0.9319	pathogenic	-0.179	Destabilizing	0.982	D	0.532	neutral	None	None	None	None	N
S/K	0.9985	likely_pathogenic	0.9985	pathogenic	-0.344	Destabilizing	0.939	D	0.319	neutral	None	None	None	None	N
S/L	0.7603	likely_pathogenic	0.7944	pathogenic	-0.179	Destabilizing	0.939	D	0.451	neutral	None	None	None	None	N
S/M	0.9125	likely_pathogenic	0.9163	pathogenic	-0.03	Destabilizing	0.997	D	0.383	neutral	None	None	None	None	N
S/N	0.9358	likely_pathogenic	0.9368	pathogenic	-0.657	Destabilizing	0.969	D	0.507	neutral	None	None	None	None	N
S/P	0.9916	likely_pathogenic	0.9935	pathogenic	-0.405	Destabilizing	0.988	D	0.466	neutral	N	0.316589176	None	None	N
S/Q	0.9893	likely_pathogenic	0.9889	pathogenic	-0.65	Destabilizing	0.997	D	0.419	neutral	None	None	None	None	N
S/R	0.9952	likely_pathogenic	0.9956	pathogenic	-0.494	Destabilizing	0.991	D	0.472	neutral	None	None	None	None	N
S/T	0.3502	ambiguous	0.3636	ambiguous	-0.599	Destabilizing	0.061	N	0.081	neutral	N	0.341320957	None	None	N
S/V	0.8273	likely_pathogenic	0.8367	pathogenic	-0.405	Destabilizing	0.939	D	0.468	neutral	None	None	None	None	N
S/W	0.9889	likely_pathogenic	0.9909	pathogenic	-1.052	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
S/Y	0.9624	likely_pathogenic	0.9695	pathogenic	-0.717	Destabilizing	0.996	D	0.537	neutral	N	0.315081153	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.