TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23329	70210;70211;70212	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
N2AB	21688	65287;65288;65289	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
N2A	20761	62506;62507;62508	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
N2B	14264	43015;43016;43017	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
Novex-1	14389	43390;43391;43392	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
Novex-2	14456	43591;43592;43593	chr2:178576147;178576146;178576145	chr2:179440874;179440873;179440872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-57
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.3462
• 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
V/M	None	None	0.002	N	0.34	0.019	0.173771789658	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	0	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
V/A	0.1183	likely_benign	0.1139	benign	-1.205	Destabilizing	0.01	N	0.303	neutral	N	0.428886666	None	None	N
V/C	0.5305	ambiguous	0.5052	ambiguous	-0.773	Destabilizing	0.624	D	0.42	neutral	None	None	None	None	N
V/D	0.1854	likely_benign	0.1775	benign	-1.155	Destabilizing	0.016	N	0.431	neutral	None	None	None	None	N
V/E	0.1358	likely_benign	0.1315	benign	-1.142	Destabilizing	None	N	0.381	neutral	N	0.342171758	None	None	N
V/F	0.124	likely_benign	0.1171	benign	-0.859	Destabilizing	0.037	N	0.491	neutral	None	None	None	None	N
V/G	0.1689	likely_benign	0.1594	benign	-1.513	Destabilizing	0.023	N	0.439	neutral	N	0.45872957	None	None	N
V/H	0.3026	likely_benign	0.2911	benign	-1.031	Destabilizing	None	N	0.431	neutral	None	None	None	None	N
V/I	0.0699	likely_benign	0.0698	benign	-0.46	Destabilizing	None	N	0.14	neutral	None	None	None	None	N
V/K	0.1796	likely_benign	0.1669	benign	-1.146	Destabilizing	None	N	0.41	neutral	None	None	None	None	N
V/L	0.099	likely_benign	0.0972	benign	-0.46	Destabilizing	None	N	0.159	neutral	N	0.426539794	None	None	N
V/M	0.0948	likely_benign	0.0895	benign	-0.419	Destabilizing	0.002	N	0.34	neutral	N	0.451995599	None	None	N
V/N	0.1282	likely_benign	0.1245	benign	-0.975	Destabilizing	0.071	N	0.555	neutral	None	None	None	None	N
V/P	0.3104	likely_benign	0.3011	benign	-0.674	Destabilizing	0.134	N	0.609	neutral	None	None	None	None	N
V/Q	0.1593	likely_benign	0.1542	benign	-1.1	Destabilizing	0.001	N	0.427	neutral	None	None	None	None	N
V/R	0.1833	likely_benign	0.1664	benign	-0.652	Destabilizing	0.037	N	0.563	neutral	None	None	None	None	N
V/S	0.1198	likely_benign	0.1157	benign	-1.427	Destabilizing	0.031	N	0.419	neutral	None	None	None	None	N
V/T	0.109	likely_benign	0.1065	benign	-1.304	Destabilizing	0.031	N	0.271	neutral	None	None	None	None	N
V/W	0.6442	likely_pathogenic	0.6073	pathogenic	-1.089	Destabilizing	0.862	D	0.512	neutral	None	None	None	None	N
V/Y	0.345	ambiguous	0.3295	benign	-0.777	Destabilizing	0.037	N	0.49	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.