TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24675	74248;74249;74250	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
N2AB	23034	69325;69326;69327	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
N2A	22107	66544;66545;66546	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
N2B	15610	47053;47054;47055	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
Novex-1	15735	47428;47429;47430	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
Novex-2	15802	47629;47630;47631	chr2:178572109;178572108;178572107	chr2:179436836;179436835;179436834
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-67
• Domain position: 60
• Structural Position: 92
• Q(SASA): 0.2478
• 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
T/S	rs1553606008	None	0.006	N	0.263	0.227	0.186928172975	gnomAD-4.0.0	1.59264E-06	None	None	None	None	I	None	0	2.28739E-05	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
T/A	0.0852	likely_benign	0.0839	benign	-0.422	Destabilizing	0.003	N	0.196	neutral	N	0.488581802	None	None	I
T/C	0.3316	likely_benign	0.3233	benign	-0.279	Destabilizing	0.823	D	0.449	neutral	None	None	None	None	I
T/D	0.457	ambiguous	0.4427	ambiguous	0.325	Stabilizing	0.013	N	0.351	neutral	None	None	None	None	I
T/E	0.3126	likely_benign	0.2968	benign	0.255	Stabilizing	0.001	N	0.164	neutral	None	None	None	None	I
T/F	0.2502	likely_benign	0.2236	benign	-0.912	Destabilizing	0.278	N	0.521	neutral	None	None	None	None	I
T/G	0.306	likely_benign	0.3019	benign	-0.555	Destabilizing	0.176	N	0.36	neutral	None	None	None	None	I
T/H	0.2319	likely_benign	0.2127	benign	-0.913	Destabilizing	0.001	N	0.309	neutral	None	None	None	None	I
T/I	0.1034	likely_benign	0.0946	benign	-0.188	Destabilizing	None	N	0.156	neutral	N	0.487251903	None	None	I
T/K	0.1842	likely_benign	0.1639	benign	-0.313	Destabilizing	None	N	0.171	neutral	None	None	None	None	I
T/L	0.0885	likely_benign	0.0856	benign	-0.188	Destabilizing	0.025	N	0.249	neutral	None	None	None	None	I
T/M	0.0832	likely_benign	0.0811	benign	0.012	Stabilizing	0.503	D	0.455	neutral	None	None	None	None	I
T/N	0.1277	likely_benign	0.1264	benign	-0.132	Destabilizing	0.045	N	0.271	neutral	N	0.475072676	None	None	I
T/P	0.3558	ambiguous	0.3743	ambiguous	-0.237	Destabilizing	0.087	N	0.452	neutral	N	0.484493652	None	None	I
T/Q	0.1877	likely_benign	0.1787	benign	-0.349	Destabilizing	0.005	N	0.224	neutral	None	None	None	None	I
T/R	0.1631	likely_benign	0.1443	benign	-0.104	Destabilizing	0.278	N	0.392	neutral	None	None	None	None	I
T/S	0.1183	likely_benign	0.1179	benign	-0.368	Destabilizing	0.006	N	0.263	neutral	N	0.485770645	None	None	I
T/V	0.0772	likely_benign	0.0742	benign	-0.237	Destabilizing	0.001	N	0.109	neutral	None	None	None	None	I
T/W	0.6852	likely_pathogenic	0.6427	pathogenic	-0.898	Destabilizing	0.984	D	0.485	neutral	None	None	None	None	I
T/Y	0.3187	likely_benign	0.3005	benign	-0.612	Destabilizing	0.01	N	0.294	neutral	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.