TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25907	77944;77945;77946	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
N2AB	24266	73021;73022;73023	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
N2A	23339	70240;70241;70242	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
N2B	16842	50749;50750;50751	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
Novex-1	16967	51124;51125;51126	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
Novex-2	17034	51325;51326;51327	chr2:178568413;178568412;178568411	chr2:179433140;179433139;179433138
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: Fn3-76
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.1265
• 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/N	None	None	0.944	N	0.523	0.275	0.270889551736	gnomAD-4.0.0	1.59253E-06	None	None	None	None	N	None	0	0	None	0	2.78443E-05	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
S/A	0.1166	likely_benign	0.1323	benign	-0.605	Destabilizing	0.818	D	0.47	neutral	None	None	None	None	N
S/C	0.1051	likely_benign	0.1049	benign	-0.932	Destabilizing	0.999	D	0.751	deleterious	D	0.524580184	None	None	N
S/D	0.7792	likely_pathogenic	0.7365	pathogenic	-1.744	Destabilizing	0.996	D	0.548	neutral	None	None	None	None	N
S/E	0.8602	likely_pathogenic	0.8272	pathogenic	-1.678	Destabilizing	0.957	D	0.522	neutral	None	None	None	None	N
S/F	0.1635	likely_benign	0.1895	benign	-0.883	Destabilizing	0.95	D	0.759	deleterious	None	None	None	None	N
S/G	0.1433	likely_benign	0.1502	benign	-0.857	Destabilizing	0.944	D	0.46	neutral	N	0.493193839	None	None	N
S/H	0.4704	ambiguous	0.417	ambiguous	-1.335	Destabilizing	0.975	D	0.781	deleterious	None	None	None	None	N
S/I	0.4046	ambiguous	0.4232	ambiguous	-0.027	Destabilizing	0.967	D	0.803	deleterious	D	0.535847584	None	None	N
S/K	0.9466	likely_pathogenic	0.9219	pathogenic	-0.653	Destabilizing	0.957	D	0.522	neutral	None	None	None	None	N
S/L	0.1999	likely_benign	0.2115	benign	-0.027	Destabilizing	0.845	D	0.692	prob.neutral	None	None	None	None	N
S/M	0.2206	likely_benign	0.2183	benign	0.111	Stabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
S/N	0.2025	likely_benign	0.1784	benign	-1.106	Destabilizing	0.944	D	0.523	neutral	N	0.476975688	None	None	N
S/P	0.9943	likely_pathogenic	0.9947	pathogenic	-0.188	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
S/Q	0.7462	likely_pathogenic	0.7006	pathogenic	-1.255	Destabilizing	0.987	D	0.652	neutral	None	None	None	None	N
S/R	0.9216	likely_pathogenic	0.8926	pathogenic	-0.575	Destabilizing	0.983	D	0.789	deleterious	N	0.506436249	None	None	N
S/T	0.1247	likely_benign	0.1232	benign	-0.844	Destabilizing	0.944	D	0.481	neutral	N	0.517177654	None	None	N
S/V	0.3485	ambiguous	0.366	ambiguous	-0.188	Destabilizing	0.975	D	0.749	deleterious	None	None	None	None	N
S/W	0.4171	ambiguous	0.4226	ambiguous	-1.027	Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	N
S/Y	0.1593	likely_benign	0.1695	benign	-0.616	Destabilizing	0.073	N	0.499	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.