TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20510	61753;61754;61755	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
N2AB	18869	56830;56831;56832	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
N2A	17942	54049;54050;54051	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
N2B	11445	34558;34559;34560	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
Novex-1	11570	34933;34934;34935	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
Novex-2	11637	35134;35135;35136	chr2:178590197;178590196;178590195	chr2:179454924;179454923;179454922
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-121
• Domain position: 32
• Structural Position: 48
• Q(SASA): 0.1386
• 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
W/R	None	None	0.997	D	0.871	0.951	0.938358567851	gnomAD-4.0.0	3.20497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74994E-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
W/A	0.9917	likely_pathogenic	0.9938	pathogenic	-2.574	Highly Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	N
W/C	0.9956	likely_pathogenic	0.9959	pathogenic	-1.611	Destabilizing	0.999	D	0.819	deleterious	D	0.70097597	None	None	N
W/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.069	Highly Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
W/E	0.9996	likely_pathogenic	0.9997	pathogenic	-2.93	Highly Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
W/F	0.442	ambiguous	0.4681	ambiguous	-1.542	Destabilizing	0.06	N	0.562	neutral	None	None	None	None	N
W/G	0.9888	likely_pathogenic	0.9923	pathogenic	-2.84	Highly Destabilizing	0.991	D	0.818	deleterious	D	0.700774166	None	None	N
W/H	0.9973	likely_pathogenic	0.9978	pathogenic	-2.14	Highly Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
W/I	0.9382	likely_pathogenic	0.9387	pathogenic	-1.579	Destabilizing	0.973	D	0.87	deleterious	None	None	None	None	N
W/K	0.9998	likely_pathogenic	0.9998	pathogenic	-2.336	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
W/L	0.902	likely_pathogenic	0.9169	pathogenic	-1.579	Destabilizing	0.885	D	0.804	deleterious	D	0.675236054	None	None	N
W/M	0.9761	likely_pathogenic	0.9778	pathogenic	-1.235	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
W/N	0.9995	likely_pathogenic	0.9997	pathogenic	-3.115	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
W/P	0.9988	likely_pathogenic	0.9992	pathogenic	-1.94	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
W/Q	0.9996	likely_pathogenic	0.9997	pathogenic	-2.829	Highly Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
W/R	0.9994	likely_pathogenic	0.9996	pathogenic	-2.358	Highly Destabilizing	0.997	D	0.871	deleterious	D	0.70097597	None	None	N
W/S	0.9958	likely_pathogenic	0.9971	pathogenic	-3.24	Highly Destabilizing	0.991	D	0.87	deleterious	D	0.70097597	None	None	N
W/T	0.9956	likely_pathogenic	0.9969	pathogenic	-3.02	Highly Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
W/V	0.9402	likely_pathogenic	0.9465	pathogenic	-1.94	Destabilizing	0.986	D	0.863	deleterious	None	None	None	None	N
W/Y	0.8967	likely_pathogenic	0.9161	pathogenic	-1.399	Destabilizing	0.91	D	0.778	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.