TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5751	17476;17477;17478	chr2:178731515;178731514;178731513	chr2:179596242;179596241;179596240
N2AB	5434	16525;16526;16527	chr2:178731515;178731514;178731513	chr2:179596242;179596241;179596240
N2A	4507	13744;13745;13746	chr2:178731515;178731514;178731513	chr2:179596242;179596241;179596240
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-41
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1146
• 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
A/T	rs759726984	-1.333	0.505	N	0.726	0.113	0.143124449307	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.92E-06	0
A/T	rs759726984	-1.333	0.505	N	0.726	0.113	0.143124449307	gnomAD-4.0.0	6.84399E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59846E-06	4.63833E-05	3.31444E-05

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
A/C	0.5227	ambiguous	0.4559	ambiguous	-1.064	Destabilizing	0.01	N	0.435	neutral	None	None	None	None	N
A/D	0.9779	likely_pathogenic	0.9696	pathogenic	-2.403	Highly Destabilizing	0.782	D	0.864	deleterious	N	0.506965368	None	None	N
A/E	0.9731	likely_pathogenic	0.9602	pathogenic	-2.195	Highly Destabilizing	0.906	D	0.818	deleterious	None	None	None	None	N
A/F	0.9195	likely_pathogenic	0.9042	pathogenic	-0.621	Destabilizing	0.967	D	0.893	deleterious	None	None	None	None	N
A/G	0.1786	likely_benign	0.1732	benign	-1.521	Destabilizing	0.001	N	0.395	neutral	N	0.450765369	None	None	N
A/H	0.9876	likely_pathogenic	0.9826	pathogenic	-2.041	Highly Destabilizing	0.991	D	0.883	deleterious	None	None	None	None	N
A/I	0.7196	likely_pathogenic	0.715	pathogenic	0.293	Stabilizing	0.826	D	0.818	deleterious	None	None	None	None	N
A/K	0.995	likely_pathogenic	0.992	pathogenic	-1.164	Destabilizing	0.826	D	0.821	deleterious	None	None	None	None	N
A/L	0.6631	likely_pathogenic	0.6258	pathogenic	0.293	Stabilizing	0.404	N	0.817	deleterious	None	None	None	None	N
A/M	0.7089	likely_pathogenic	0.6914	pathogenic	0.029	Stabilizing	0.991	D	0.804	deleterious	None	None	None	None	N
A/N	0.9362	likely_pathogenic	0.9181	pathogenic	-1.483	Destabilizing	0.826	D	0.879	deleterious	None	None	None	None	N
A/P	0.9896	likely_pathogenic	0.9838	pathogenic	-0.104	Destabilizing	0.879	D	0.817	deleterious	N	0.506965368	None	None	N
A/Q	0.9726	likely_pathogenic	0.9622	pathogenic	-1.268	Destabilizing	0.906	D	0.803	deleterious	None	None	None	None	N
A/R	0.9883	likely_pathogenic	0.9812	pathogenic	-1.289	Destabilizing	0.906	D	0.806	deleterious	None	None	None	None	N
A/S	0.2192	likely_benign	0.2349	benign	-1.875	Destabilizing	0.338	N	0.679	prob.neutral	N	0.444666116	None	None	N
A/T	0.2045	likely_benign	0.1928	benign	-1.541	Destabilizing	0.505	D	0.726	prob.delet.	N	0.469004413	None	None	N
A/V	0.3282	likely_benign	0.3153	benign	-0.104	Destabilizing	0.505	D	0.718	prob.delet.	N	0.447298202	None	None	N
A/W	0.9919	likely_pathogenic	0.9899	pathogenic	-1.47	Destabilizing	0.991	D	0.895	deleterious	None	None	None	None	N
A/Y	0.9662	likely_pathogenic	0.9548	pathogenic	-0.881	Destabilizing	0.967	D	0.896	deleterious	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.