TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25718	77377;77378;77379	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
N2AB	24077	72454;72455;72456	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
N2A	23150	69673;69674;69675	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
N2B	16653	50182;50183;50184	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
Novex-1	16778	50557;50558;50559	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
Novex-2	16845	50758;50759;50760	chr2:178568980;178568979;178568978	chr2:179433707;179433706;179433705
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-75
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1986
• 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
S/I	rs1439934941	0.375	0.999	N	0.615	0.414	0.50685403127	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/I	rs1439934941	0.375	0.999	N	0.615	0.414	0.50685403127	gnomAD-4.0.0	6.57748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47115E-05	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
S/A	0.0855	likely_benign	0.0798	benign	-0.742	Destabilizing	0.034	N	0.194	neutral	None	None	None	None	N
S/C	0.0961	likely_benign	0.0893	benign	-0.605	Destabilizing	1.0	D	0.589	neutral	N	0.508206994	None	None	N
S/D	0.5434	ambiguous	0.4967	ambiguous	-1.027	Destabilizing	0.994	D	0.427	neutral	None	None	None	None	N
S/E	0.5733	likely_pathogenic	0.5273	ambiguous	-0.917	Destabilizing	0.98	D	0.361	neutral	None	None	None	None	N
S/F	0.2158	likely_benign	0.1934	benign	-0.765	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
S/G	0.1089	likely_benign	0.1009	benign	-1.084	Destabilizing	0.98	D	0.361	neutral	N	0.491797806	None	None	N
S/H	0.248	likely_benign	0.2287	benign	-1.585	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
S/I	0.1611	likely_benign	0.147	benign	0.089	Stabilizing	0.999	D	0.615	neutral	N	0.503180565	None	None	N
S/K	0.5581	ambiguous	0.5222	ambiguous	-0.476	Destabilizing	0.638	D	0.164	neutral	None	None	None	None	N
S/L	0.1108	likely_benign	0.0999	benign	0.089	Stabilizing	0.997	D	0.489	neutral	None	None	None	None	N
S/M	0.1741	likely_benign	0.1712	benign	0.17	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
S/N	0.1346	likely_benign	0.1228	benign	-0.891	Destabilizing	0.938	D	0.453	neutral	D	0.528605369	None	None	N
S/P	0.9687	likely_pathogenic	0.9586	pathogenic	-0.152	Destabilizing	0.994	D	0.578	neutral	None	None	None	None	N
S/Q	0.4041	ambiguous	0.3844	ambiguous	-0.833	Destabilizing	0.997	D	0.487	neutral	None	None	None	None	N
S/R	0.4408	ambiguous	0.3973	ambiguous	-0.654	Destabilizing	0.425	N	0.379	neutral	N	0.475526749	None	None	N
S/T	0.0748	likely_benign	0.0736	benign	-0.673	Destabilizing	0.09	N	0.196	neutral	N	0.504765717	None	None	N
S/V	0.1841	likely_benign	0.1701	benign	-0.152	Destabilizing	0.992	D	0.523	neutral	None	None	None	None	N
S/W	0.4057	ambiguous	0.3694	ambiguous	-0.913	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
S/Y	0.2186	likely_benign	0.1966	benign	-0.523	Destabilizing	1.0	D	0.625	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.