TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15720	47383;47384;47385	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
N2AB	14079	42460;42461;42462	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
N2A	13152	39679;39680;39681	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
N2B	6655	20188;20189;20190	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
Novex-1	6780	20563;20564;20565	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
Novex-2	6847	20764;20765;20766	chr2:178618300;178618299;178618298	chr2:179483027;179483026;179483025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-1
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.4957
• 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/A	None	None	0.984	D	0.587	0.439	0.369682402691	gnomAD-4.0.0	1.36922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79976E-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
G/A	0.3371	likely_benign	0.3326	benign	-0.311	Destabilizing	0.984	D	0.587	neutral	D	0.639502831	None	None	N
G/C	0.6632	likely_pathogenic	0.5638	ambiguous	-0.93	Destabilizing	1.0	D	0.745	deleterious	D	0.717634206	None	None	N
G/D	0.528	ambiguous	0.4963	ambiguous	-0.608	Destabilizing	0.996	D	0.721	prob.delet.	N	0.471195019	None	None	N
G/E	0.6683	likely_pathogenic	0.6569	pathogenic	-0.761	Destabilizing	0.997	D	0.735	prob.delet.	None	None	None	None	N
G/F	0.9142	likely_pathogenic	0.9253	pathogenic	-0.991	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/H	0.7795	likely_pathogenic	0.7333	pathogenic	-0.499	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
G/I	0.8419	likely_pathogenic	0.8417	pathogenic	-0.428	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
G/K	0.8609	likely_pathogenic	0.8313	pathogenic	-0.859	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
G/L	0.8481	likely_pathogenic	0.8433	pathogenic	-0.428	Destabilizing	0.997	D	0.767	deleterious	None	None	None	None	N
G/M	0.8557	likely_pathogenic	0.8553	pathogenic	-0.549	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/N	0.4839	ambiguous	0.4051	ambiguous	-0.532	Destabilizing	0.997	D	0.746	deleterious	None	None	None	None	N
G/P	0.9495	likely_pathogenic	0.9469	pathogenic	-0.356	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
G/Q	0.7158	likely_pathogenic	0.6811	pathogenic	-0.803	Destabilizing	0.997	D	0.761	deleterious	None	None	None	None	N
G/R	0.7727	likely_pathogenic	0.7472	pathogenic	-0.399	Destabilizing	0.513	D	0.521	neutral	D	0.534366686	None	None	N
G/S	0.2099	likely_benign	0.2042	benign	-0.679	Destabilizing	0.996	D	0.745	deleterious	N	0.478613799	None	None	N
G/T	0.478	ambiguous	0.4368	ambiguous	-0.759	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	N
G/V	0.7106	likely_pathogenic	0.7052	pathogenic	-0.356	Destabilizing	0.998	D	0.777	deleterious	D	0.717533046	None	None	N
G/W	0.8637	likely_pathogenic	0.8667	pathogenic	-1.147	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
G/Y	0.842	likely_pathogenic	0.8368	pathogenic	-0.799	Destabilizing	1.0	D	0.789	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.