TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25808	77647;77648;77649	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
N2AB	24167	72724;72725;72726	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
N2A	23240	69943;69944;69945	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
N2B	16743	50452;50453;50454	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
Novex-1	16868	50827;50828;50829	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
Novex-2	16935	51028;51029;51030	chr2:178568710;178568709;178568708	chr2:179433437;179433436;179433435
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: Ig-136
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4117
• 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/R	rs1415635107	None	0.056	D	0.291	0.328	0.295974979623	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/R	rs1415635107	None	0.056	D	0.291	0.328	0.295974979623	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-05	0	0
S/T	None	None	0.892	N	0.389	0.273	0.282575091529	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

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	0.13	likely_benign	0.1028	benign	-0.167	Destabilizing	0.818	D	0.394	neutral	None	None	None	None	N
S/C	0.1592	likely_benign	0.1326	benign	-0.368	Destabilizing	0.999	D	0.543	neutral	N	0.509040958	None	None	N
S/D	0.8235	likely_pathogenic	0.845	pathogenic	0.503	Stabilizing	0.957	D	0.464	neutral	None	None	None	None	N
S/E	0.8863	likely_pathogenic	0.8826	pathogenic	0.429	Stabilizing	0.916	D	0.415	neutral	None	None	None	None	N
S/F	0.3987	ambiguous	0.3198	benign	-0.806	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	N
S/G	0.1624	likely_benign	0.1658	benign	-0.273	Destabilizing	0.892	D	0.367	neutral	N	0.508027	None	None	N
S/H	0.4965	ambiguous	0.4896	ambiguous	-0.654	Destabilizing	0.997	D	0.549	neutral	None	None	None	None	N
S/I	0.2859	likely_benign	0.2738	benign	-0.025	Destabilizing	0.983	D	0.607	neutral	N	0.507585096	None	None	N
S/K	0.9282	likely_pathogenic	0.9245	pathogenic	-0.222	Destabilizing	0.845	D	0.376	neutral	None	None	None	None	N
S/L	0.1694	likely_benign	0.143	benign	-0.025	Destabilizing	0.916	D	0.521	neutral	None	None	None	None	N
S/M	0.2619	likely_benign	0.2357	benign	-0.119	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
S/N	0.2037	likely_benign	0.237	benign	-0.101	Destabilizing	0.892	D	0.467	neutral	N	0.515049787	None	None	N
S/P	0.6461	likely_pathogenic	0.607	pathogenic	-0.044	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
S/Q	0.7252	likely_pathogenic	0.7082	pathogenic	-0.236	Destabilizing	0.975	D	0.523	neutral	None	None	None	None	N
S/R	0.8802	likely_pathogenic	0.874	pathogenic	-0.095	Destabilizing	0.056	N	0.291	neutral	D	0.527805653	None	None	N
S/T	0.0973	likely_benign	0.0968	benign	-0.18	Destabilizing	0.892	D	0.389	neutral	N	0.456020126	None	None	N
S/V	0.2672	likely_benign	0.2366	benign	-0.044	Destabilizing	0.987	D	0.574	neutral	None	None	None	None	N
S/W	0.5768	likely_pathogenic	0.5174	ambiguous	-0.882	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
S/Y	0.3511	ambiguous	0.3065	benign	-0.539	Destabilizing	0.996	D	0.603	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.