TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30996	93211;93212;93213	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
N2AB	29355	88288;88289;88290	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
N2A	28428	85507;85508;85509	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
N2B	21931	66016;66017;66018	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
Novex-1	22056	66391;66392;66393	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
Novex-2	22123	66592;66593;66594	chr2:178548640;178548639;178548638	chr2:179413367;179413366;179413365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-150
• Domain position: 70
• Structural Position: 156
• Q(SASA): 0.0948
• 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
L/F	rs1698155054	None	0.002	N	0.419	0.152	0.322510055762	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/P	rs751341499	-1.267	0.916	N	0.853	0.62	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/P	rs751341499	-1.267	0.916	N	0.853	0.62	None	gnomAD-4.0.0	5.47345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39668E-06	0	3.31312E-05

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
L/A	0.8155	likely_pathogenic	0.809	pathogenic	-2.405	Highly Destabilizing	0.399	N	0.755	deleterious	None	None	None	None	N
L/C	0.5674	likely_pathogenic	0.5546	ambiguous	-2.046	Highly Destabilizing	0.982	D	0.761	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9979	pathogenic	-2.501	Highly Destabilizing	0.935	D	0.852	deleterious	None	None	None	None	N
L/E	0.991	likely_pathogenic	0.9891	pathogenic	-2.225	Highly Destabilizing	0.826	D	0.842	deleterious	None	None	None	None	N
L/F	0.1257	likely_benign	0.1235	benign	-1.451	Destabilizing	0.002	N	0.419	neutral	N	0.480886714	None	None	N
L/G	0.9663	likely_pathogenic	0.9597	pathogenic	-2.987	Highly Destabilizing	0.826	D	0.841	deleterious	None	None	None	None	N
L/H	0.9394	likely_pathogenic	0.9291	pathogenic	-2.594	Highly Destabilizing	0.931	D	0.853	deleterious	N	0.49392854	None	None	N
L/I	0.1242	likely_benign	0.1388	benign	-0.699	Destabilizing	0.201	N	0.676	prob.neutral	N	0.454514963	None	None	N
L/K	0.9822	likely_pathogenic	0.9794	pathogenic	-1.622	Destabilizing	0.826	D	0.829	deleterious	None	None	None	None	N
L/M	0.1593	likely_benign	0.1599	benign	-1.017	Destabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	N
L/N	0.984	likely_pathogenic	0.9813	pathogenic	-2.091	Highly Destabilizing	0.935	D	0.854	deleterious	None	None	None	None	N
L/P	0.9949	likely_pathogenic	0.9947	pathogenic	-1.251	Destabilizing	0.916	D	0.853	deleterious	N	0.49392854	None	None	N
L/Q	0.9427	likely_pathogenic	0.9301	pathogenic	-1.834	Destabilizing	0.935	D	0.839	deleterious	None	None	None	None	N
L/R	0.9605	likely_pathogenic	0.954	pathogenic	-1.63	Destabilizing	0.781	D	0.833	deleterious	N	0.49392854	None	None	N
L/S	0.9685	likely_pathogenic	0.9656	pathogenic	-2.842	Highly Destabilizing	0.826	D	0.823	deleterious	None	None	None	None	N
L/T	0.9246	likely_pathogenic	0.9185	pathogenic	-2.398	Highly Destabilizing	0.826	D	0.766	deleterious	None	None	None	None	N
L/V	0.1333	likely_benign	0.1447	benign	-1.251	Destabilizing	0.201	N	0.693	prob.neutral	N	0.461363577	None	None	N
L/W	0.788	likely_pathogenic	0.7778	pathogenic	-1.769	Destabilizing	0.947	D	0.835	deleterious	None	None	None	None	N
L/Y	0.6845	likely_pathogenic	0.668	pathogenic	-1.486	Destabilizing	0.539	D	0.766	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.