TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30625	92098;92099;92100	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
N2AB	28984	87175;87176;87177	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
N2A	28057	84394;84395;84396	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
N2B	21560	64903;64904;64905	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
Novex-1	21685	65278;65279;65280	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
Novex-2	21752	65479;65480;65481	chr2:178549849;178549848;178549847	chr2:179414576;179414575;179414574
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-111
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.2695
• 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
G/R	None	None	1.0	N	0.677	0.607	0.586724321019	gnomAD-4.0.0	1.69565E-06	None	None	None	None	N	None	0	0	None	0	2.80599E-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
G/A	0.381	ambiguous	0.4515	ambiguous	-0.376	Destabilizing	1.0	D	0.638	neutral	N	0.473279844	None	None	N
G/C	0.7105	likely_pathogenic	0.7776	pathogenic	-0.887	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
G/D	0.8543	likely_pathogenic	0.8832	pathogenic	-0.738	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/E	0.8259	likely_pathogenic	0.8603	pathogenic	-0.878	Destabilizing	1.0	D	0.704	prob.neutral	N	0.495143081	None	None	N
G/F	0.9268	likely_pathogenic	0.9437	pathogenic	-0.955	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
G/H	0.9466	likely_pathogenic	0.9594	pathogenic	-0.669	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
G/I	0.8942	likely_pathogenic	0.9091	pathogenic	-0.392	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
G/K	0.9428	likely_pathogenic	0.953	pathogenic	-1.041	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/L	0.874	likely_pathogenic	0.9007	pathogenic	-0.392	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
G/M	0.9277	likely_pathogenic	0.9465	pathogenic	-0.495	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/N	0.8845	likely_pathogenic	0.9053	pathogenic	-0.645	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
G/P	0.928	likely_pathogenic	0.9296	pathogenic	-0.351	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
G/Q	0.9089	likely_pathogenic	0.9298	pathogenic	-0.911	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
G/R	0.9125	likely_pathogenic	0.9298	pathogenic	-0.579	Destabilizing	1.0	D	0.677	prob.neutral	N	0.496157039	None	None	N
G/S	0.3915	ambiguous	0.4515	ambiguous	-0.796	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
G/T	0.7394	likely_pathogenic	0.773	pathogenic	-0.865	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
G/V	0.825	likely_pathogenic	0.8541	pathogenic	-0.351	Destabilizing	1.0	D	0.682	prob.neutral	N	0.506325257	None	None	N
G/W	0.9042	likely_pathogenic	0.9183	pathogenic	-1.15	Destabilizing	1.0	D	0.664	neutral	D	0.524683002	None	None	N
G/Y	0.8965	likely_pathogenic	0.9185	pathogenic	-0.798	Destabilizing	1.0	D	0.634	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.