TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31602	95029;95030;95031	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
N2AB	29961	90106;90107;90108	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
N2A	29034	87325;87326;87327	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
N2B	22537	67834;67835;67836	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
Novex-1	22662	68209;68210;68211	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
Novex-2	22729	68410;68411;68412	chr2:178546624;178546623;178546622	chr2:179411351;179411350;179411349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-118
• Domain position: 97
• Structural Position: 126
• Q(SASA): 0.4283
• 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
P/S	rs1697282371	None	0.376	N	0.465	0.15	0.294206760003	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs1697282371	None	0.376	N	0.465	0.15	0.294206760003	gnomAD-4.0.0	2.56835E-06	None	None	None	None	N	None	3.38581E-05	0	None	0	0	None	0	0	0	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	0.0691	likely_benign	0.0675	benign	-0.637	Destabilizing	0.002	N	0.357	neutral	N	0.501527837	None	None	N
P/C	0.5054	ambiguous	0.5076	ambiguous	-0.716	Destabilizing	0.977	D	0.669	prob.neutral	None	None	None	None	N
P/D	0.5413	ambiguous	0.54	ambiguous	-0.373	Destabilizing	0.444	N	0.459	neutral	None	None	None	None	N
P/E	0.3174	likely_benign	0.3165	benign	-0.479	Destabilizing	0.011	N	0.42	neutral	None	None	None	None	N
P/F	0.4359	ambiguous	0.4259	ambiguous	-0.771	Destabilizing	0.848	D	0.68	prob.neutral	None	None	None	None	N
P/G	0.3548	ambiguous	0.3365	benign	-0.796	Destabilizing	0.444	N	0.556	neutral	None	None	None	None	N
P/H	0.2525	likely_benign	0.2525	benign	-0.301	Destabilizing	0.97	D	0.633	neutral	D	0.524160612	None	None	N
P/I	0.2688	likely_benign	0.2495	benign	-0.365	Destabilizing	0.737	D	0.647	neutral	None	None	None	None	N
P/K	0.3194	likely_benign	0.3205	benign	-0.54	Destabilizing	0.444	N	0.455	neutral	None	None	None	None	N
P/L	0.112	likely_benign	0.1045	benign	-0.365	Destabilizing	0.004	N	0.665	prob.neutral	N	0.480252647	None	None	N
P/M	0.2527	likely_benign	0.238	benign	-0.35	Destabilizing	0.955	D	0.637	neutral	None	None	None	None	N
P/N	0.3783	ambiguous	0.3572	ambiguous	-0.306	Destabilizing	0.848	D	0.648	neutral	None	None	None	None	N
P/Q	0.1882	likely_benign	0.1883	benign	-0.565	Destabilizing	0.737	D	0.485	neutral	None	None	None	None	N
P/R	0.2123	likely_benign	0.2154	benign	0.02	Stabilizing	0.808	D	0.623	neutral	N	0.505549378	None	None	N
P/S	0.1402	likely_benign	0.1359	benign	-0.71	Destabilizing	0.376	N	0.465	neutral	N	0.46445257	None	None	N
P/T	0.1098	likely_benign	0.1029	benign	-0.712	Destabilizing	0.546	D	0.437	neutral	N	0.463211575	None	None	N
P/V	0.1786	likely_benign	0.1698	benign	-0.42	Destabilizing	0.444	N	0.56	neutral	None	None	None	None	N
P/W	0.667	likely_pathogenic	0.6666	pathogenic	-0.836	Destabilizing	0.992	D	0.665	prob.neutral	None	None	None	None	N
P/Y	0.4701	ambiguous	0.4561	ambiguous	-0.541	Destabilizing	0.972	D	0.681	prob.neutral	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.