TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30758	92497;92498;92499	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
N2AB	29117	87574;87575;87576	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
N2A	28190	84793;84794;84795	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
N2B	21693	65302;65303;65304	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
Novex-1	21818	65677;65678;65679	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
Novex-2	21885	65878;65879;65880	chr2:178549354;178549353;178549352	chr2:179414081;179414080;179414079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-112
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2866
• 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
R/K	None	None	0.997	N	0.729	0.317	0.348324211639	gnomAD-4.0.0	3.42095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49724E-06	0	0
R/S	None	None	1.0	N	0.817	0.327	0.303123707472	gnomAD-4.0.0	6.84182E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99444E-07	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
R/A	0.9663	likely_pathogenic	0.9713	pathogenic	-2.195	Highly Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
R/C	0.5037	ambiguous	0.5294	ambiguous	-2.184	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/D	0.9965	likely_pathogenic	0.9967	pathogenic	-1.734	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
R/E	0.947	likely_pathogenic	0.9482	pathogenic	-1.475	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
R/F	0.9473	likely_pathogenic	0.9514	pathogenic	-1.269	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
R/G	0.9408	likely_pathogenic	0.9439	pathogenic	-2.565	Highly Destabilizing	1.0	D	0.827	deleterious	N	0.477863245	None	None	N
R/H	0.4438	ambiguous	0.435	ambiguous	-1.781	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
R/I	0.8195	likely_pathogenic	0.8489	pathogenic	-1.092	Destabilizing	1.0	D	0.841	deleterious	N	0.465555433	None	None	N
R/K	0.1827	likely_benign	0.1831	benign	-1.23	Destabilizing	0.997	D	0.729	prob.delet.	N	0.395901882	None	None	N
R/L	0.7489	likely_pathogenic	0.7731	pathogenic	-1.092	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
R/M	0.7676	likely_pathogenic	0.7948	pathogenic	-1.558	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
R/N	0.9865	likely_pathogenic	0.9877	pathogenic	-1.984	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
R/P	0.9981	likely_pathogenic	0.9978	pathogenic	-1.453	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
R/Q	0.3479	ambiguous	0.356	ambiguous	-1.741	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
R/S	0.9818	likely_pathogenic	0.985	pathogenic	-2.79	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.466822881	None	None	N
R/T	0.947	likely_pathogenic	0.9543	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.821	deleterious	N	0.471747178	None	None	N
R/V	0.875	likely_pathogenic	0.8895	pathogenic	-1.453	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
R/W	0.6509	likely_pathogenic	0.6592	pathogenic	-0.748	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
R/Y	0.8226	likely_pathogenic	0.8348	pathogenic	-0.707	Destabilizing	1.0	D	0.854	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.