TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33730	101413;101414;101415	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
N2AB	32089	96490;96491;96492	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
N2A	31162	93709;93710;93711	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
N2B	24665	74218;74219;74220	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
Novex-1	24790	74593;74594;74595	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
Novex-2	24857	74794;74795;74796	chr2:178535427;178535426;178535425	chr2:179400154;179400153;179400152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-132
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.1849
• 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
A/V	rs1690988435	None	0.999	N	0.564	0.355	0.377097596864	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
A/V	rs1690988435	None	0.999	N	0.564	0.355	0.377097596864	gnomAD-4.0.0	2.56211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.68025E-05	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
A/C	0.797	likely_pathogenic	0.7083	pathogenic	-1.004	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/D	0.9307	likely_pathogenic	0.7958	pathogenic	-0.885	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/E	0.8725	likely_pathogenic	0.6836	pathogenic	-0.96	Destabilizing	1.0	D	0.691	prob.neutral	N	0.335717428	None	None	N
A/F	0.8666	likely_pathogenic	0.7272	pathogenic	-1.226	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/G	0.4631	ambiguous	0.359	ambiguous	-1.085	Destabilizing	0.99	D	0.469	neutral	N	0.429803811	None	None	N
A/H	0.9078	likely_pathogenic	0.822	pathogenic	-1.191	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
A/I	0.76	likely_pathogenic	0.5892	pathogenic	-0.531	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
A/K	0.9607	likely_pathogenic	0.8831	pathogenic	-0.972	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
A/L	0.5276	ambiguous	0.3583	ambiguous	-0.531	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
A/M	0.6705	likely_pathogenic	0.5219	ambiguous	-0.449	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/N	0.7468	likely_pathogenic	0.5966	pathogenic	-0.66	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
A/P	0.2013	likely_benign	0.2023	benign	-0.612	Destabilizing	0.604	D	0.323	neutral	N	0.39792068	None	None	N
A/Q	0.75	likely_pathogenic	0.61	pathogenic	-0.893	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
A/R	0.9193	likely_pathogenic	0.8101	pathogenic	-0.615	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/S	0.1881	likely_benign	0.148	benign	-1.024	Destabilizing	0.986	D	0.487	neutral	N	0.380028352	None	None	N
A/T	0.3458	ambiguous	0.2279	benign	-1.007	Destabilizing	0.998	D	0.631	neutral	N	0.370139432	None	None	N
A/V	0.5018	ambiguous	0.3381	benign	-0.612	Destabilizing	0.999	D	0.564	neutral	N	0.429803811	None	None	N
A/W	0.9837	likely_pathogenic	0.957	pathogenic	-1.439	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/Y	0.9432	likely_pathogenic	0.8603	pathogenic	-1.06	Destabilizing	1.0	D	0.785	deleterious	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.