TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32896	98911;98912;98913	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
N2AB	31255	93988;93989;93990	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
N2A	30328	91207;91208;91209	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
N2B	23831	71716;71717;71718	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
Novex-1	23956	72091;72092;72093	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
Novex-2	24023	72292;72293;72294	chr2:178539249;178539248;178539247	chr2:179403976;179403975;179403974
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: Fn3-128
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.1254
• Predicted PPI site: I

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/L	rs1335232513	None	0.972	N	0.73	0.236	0.468420198123	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1335232513	None	0.972	N	0.73	0.236	0.468420198123	gnomAD-4.0.0	4.34111E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.93764E-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
P/A	0.1148	likely_benign	0.1067	benign	-0.694	Destabilizing	0.908	D	0.725	deleterious	N	0.506336224	None	None	I
P/C	0.604	likely_pathogenic	0.5632	ambiguous	-0.701	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/D	0.8823	likely_pathogenic	0.8964	pathogenic	-0.375	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I
P/E	0.5371	ambiguous	0.543	ambiguous	-0.489	Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	I
P/F	0.7635	likely_pathogenic	0.7533	pathogenic	-0.965	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	I
P/G	0.7041	likely_pathogenic	0.6786	pathogenic	-0.831	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	I
P/H	0.5054	ambiguous	0.4815	ambiguous	-0.358	Destabilizing	0.999	D	0.827	deleterious	N	0.488508307	None	None	I
P/I	0.2457	likely_benign	0.2338	benign	-0.48	Destabilizing	0.979	D	0.709	prob.delet.	None	None	None	None	I
P/K	0.4397	ambiguous	0.4243	ambiguous	-0.389	Destabilizing	0.995	D	0.814	deleterious	None	None	None	None	I
P/L	0.2272	likely_benign	0.2124	benign	-0.48	Destabilizing	0.972	D	0.73	deleterious	N	0.462082259	None	None	I
P/M	0.4355	ambiguous	0.4049	ambiguous	-0.315	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	I
P/N	0.7349	likely_pathogenic	0.7361	pathogenic	-0.157	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	I
P/Q	0.3226	likely_benign	0.3063	benign	-0.464	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
P/R	0.3301	likely_benign	0.3057	benign	0.156	Stabilizing	0.998	D	0.774	deleterious	N	0.510357964	None	None	I
P/S	0.2969	likely_benign	0.2793	benign	-0.579	Destabilizing	0.993	D	0.821	deleterious	N	0.469897073	None	None	I
P/T	0.1892	likely_benign	0.1787	benign	-0.595	Destabilizing	0.986	D	0.841	deleterious	N	0.46337616	None	None	I
P/V	0.1747	likely_benign	0.1599	benign	-0.517	Destabilizing	0.159	N	0.459	neutral	None	None	None	None	I
P/W	0.9178	likely_pathogenic	0.9154	pathogenic	-0.99	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/Y	0.778	likely_pathogenic	0.7702	pathogenic	-0.675	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I

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.