TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23283	70072;70073;70074	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
N2AB	21642	65149;65150;65151	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
N2A	20715	62368;62369;62370	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
N2B	14218	42877;42878;42879	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
Novex-1	14343	43252;43253;43254	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
Novex-2	14410	43453;43454;43455	chr2:178576285;178576284;178576283	chr2:179441012;179441011;179441010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-57
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.526
• 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	0.709	0.431	0.545045102275	gnomAD-4.0.0	6.89601E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03215E-07	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	0.1867	likely_benign	0.226	benign	-0.285	Destabilizing	1.0	D	0.521	neutral	N	0.477235042	None	None	N
G/C	0.2861	likely_benign	0.3248	benign	-0.968	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/D	0.1531	likely_benign	0.1867	benign	-0.809	Destabilizing	0.921	D	0.516	neutral	None	None	None	None	N
G/E	0.2005	likely_benign	0.2396	benign	-0.974	Destabilizing	1.0	D	0.696	prob.neutral	N	0.473067532	None	None	N
G/F	0.6969	likely_pathogenic	0.7628	pathogenic	-1.043	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/H	0.4033	ambiguous	0.4718	ambiguous	-0.368	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/I	0.4507	ambiguous	0.5351	ambiguous	-0.518	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/K	0.3857	ambiguous	0.448	ambiguous	-0.836	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
G/L	0.5442	ambiguous	0.6089	pathogenic	-0.518	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
G/M	0.5485	ambiguous	0.6188	pathogenic	-0.647	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/N	0.2171	likely_benign	0.2612	benign	-0.495	Destabilizing	1.0	D	0.572	neutral	None	None	None	None	N
G/P	0.8152	likely_pathogenic	0.8663	pathogenic	-0.413	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
G/Q	0.3378	likely_benign	0.39	ambiguous	-0.799	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
G/R	0.3318	likely_benign	0.3854	ambiguous	-0.333	Destabilizing	1.0	D	0.709	prob.delet.	N	0.494730186	None	None	N
G/S	0.1264	likely_benign	0.1458	benign	-0.605	Destabilizing	1.0	D	0.56	neutral	None	None	None	None	N
G/T	0.1827	likely_benign	0.2327	benign	-0.71	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
G/V	0.3301	likely_benign	0.4023	ambiguous	-0.413	Destabilizing	1.0	D	0.739	prob.delet.	N	0.484641329	None	None	N
G/W	0.5508	ambiguous	0.6016	pathogenic	-1.149	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/Y	0.5713	likely_pathogenic	0.6375	pathogenic	-0.839	Destabilizing	1.0	D	0.729	prob.delet.	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.