TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28663	86212;86213;86214	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
N2AB	27022	81289;81290;81291	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
N2A	26095	78508;78509;78510	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
N2B	19598	59017;59018;59019	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
Novex-1	19723	59392;59393;59394	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
Novex-2	19790	59593;59594;59595	chr2:178560145;178560144;178560143	chr2:179424872;179424871;179424870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-97
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2952
• 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/L	None	None	0.698	N	0.579	0.225	0.497214377195	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85891E-06	0	0
S/T	None	None	0.014	N	0.35	0.111	0.110078149338	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1118	likely_benign	0.0983	benign	-0.192	Destabilizing	0.489	N	0.457	neutral	N	0.456603624	None	None	N
S/C	0.092	likely_benign	0.0942	benign	-0.733	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
S/D	0.8453	likely_pathogenic	0.8328	pathogenic	-1.757	Destabilizing	0.86	D	0.519	neutral	None	None	None	None	N
S/E	0.8629	likely_pathogenic	0.8402	pathogenic	-1.745	Destabilizing	0.86	D	0.527	neutral	None	None	None	None	N
S/F	0.2309	likely_benign	0.244	benign	-0.828	Destabilizing	0.915	D	0.617	neutral	None	None	None	None	N
S/G	0.1903	likely_benign	0.1634	benign	-0.355	Destabilizing	0.86	D	0.501	neutral	None	None	None	None	N
S/H	0.4395	ambiguous	0.4674	ambiguous	-0.949	Destabilizing	0.956	D	0.621	neutral	None	None	None	None	N
S/I	0.2394	likely_benign	0.1994	benign	0.128	Stabilizing	0.956	D	0.616	neutral	None	None	None	None	N
S/K	0.8923	likely_pathogenic	0.876	pathogenic	-0.367	Destabilizing	0.86	D	0.525	neutral	None	None	None	None	N
S/L	0.159	likely_benign	0.1459	benign	0.128	Stabilizing	0.698	D	0.579	neutral	N	0.474130592	None	None	N
S/M	0.2705	likely_benign	0.2555	benign	0.321	Stabilizing	0.998	D	0.605	neutral	None	None	None	None	N
S/N	0.3422	ambiguous	0.3307	benign	-0.77	Destabilizing	0.86	D	0.522	neutral	None	None	None	None	N
S/P	0.8898	likely_pathogenic	0.8664	pathogenic	0.05	Stabilizing	0.97	D	0.613	neutral	N	0.493295143	None	None	N
S/Q	0.7279	likely_pathogenic	0.7136	pathogenic	-1.086	Destabilizing	0.978	D	0.555	neutral	None	None	None	None	N
S/R	0.8158	likely_pathogenic	0.7985	pathogenic	-0.189	Destabilizing	0.956	D	0.62	neutral	None	None	None	None	N
S/T	0.0897	likely_benign	0.0813	benign	-0.488	Destabilizing	0.014	N	0.35	neutral	N	0.435150916	None	None	N
S/V	0.2373	likely_benign	0.2057	benign	0.05	Stabilizing	0.754	D	0.576	neutral	None	None	None	None	N
S/W	0.3608	ambiguous	0.4253	ambiguous	-0.988	Destabilizing	0.994	D	0.703	prob.neutral	None	None	None	None	N
S/Y	0.1776	likely_benign	0.2102	benign	-0.522	Destabilizing	0.043	N	0.405	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.