TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23294	70105;70106;70107	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
N2AB	21653	65182;65183;65184	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
N2A	20726	62401;62402;62403	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
N2B	14229	42910;42911;42912	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
Novex-1	14354	43285;43286;43287	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
Novex-2	14421	43486;43487;43488	chr2:178576252;178576251;178576250	chr2:179440979;179440978;179440977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-57
• Domain position: 55
• Structural Position: 72
• Q(SASA): 0.4273
• Predicted PPI site: I

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
T/I	None	None	0.007	N	0.233	0.251	0.301789629655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	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
T/A	0.0778	likely_benign	0.079	benign	-0.189	Destabilizing	0.003	N	0.096	neutral	N	0.487443819	None	None	I
T/C	0.4212	ambiguous	0.3931	ambiguous	-0.409	Destabilizing	0.94	D	0.354	neutral	None	None	None	None	I
T/D	0.3174	likely_benign	0.3048	benign	-0.049	Destabilizing	0.418	N	0.342	neutral	None	None	None	None	I
T/E	0.2416	likely_benign	0.2371	benign	-0.144	Destabilizing	0.418	N	0.352	neutral	None	None	None	None	I
T/F	0.2741	likely_benign	0.2485	benign	-0.88	Destabilizing	0.002	N	0.282	neutral	None	None	None	None	I
T/G	0.2102	likely_benign	0.1907	benign	-0.222	Destabilizing	0.129	N	0.349	neutral	None	None	None	None	I
T/H	0.2322	likely_benign	0.2147	benign	-0.399	Destabilizing	0.836	D	0.358	neutral	None	None	None	None	I
T/I	0.2023	likely_benign	0.1969	benign	-0.22	Destabilizing	0.007	N	0.233	neutral	N	0.452891315	None	None	I
T/K	0.1709	likely_benign	0.1646	benign	-0.304	Destabilizing	0.418	N	0.353	neutral	None	None	None	None	I
T/L	0.1099	likely_benign	0.1049	benign	-0.22	Destabilizing	0.129	N	0.396	neutral	None	None	None	None	I
T/M	0.0981	likely_benign	0.1015	benign	-0.218	Destabilizing	0.836	D	0.367	neutral	None	None	None	None	I
T/N	0.1071	likely_benign	0.1078	benign	-0.116	Destabilizing	0.351	N	0.321	neutral	N	0.499199608	None	None	I
T/P	0.0929	likely_benign	0.1008	benign	-0.189	Destabilizing	0.002	N	0.236	neutral	N	0.469839493	None	None	I
T/Q	0.184	likely_benign	0.1807	benign	-0.311	Destabilizing	0.716	D	0.443	neutral	None	None	None	None	I
T/R	0.1785	likely_benign	0.1731	benign	-0.06	Destabilizing	0.716	D	0.455	neutral	None	None	None	None	I
T/S	0.1001	likely_benign	0.095	benign	-0.268	Destabilizing	0.003	N	0.095	neutral	N	0.487617177	None	None	I
T/V	0.1516	likely_benign	0.1441	benign	-0.189	Destabilizing	0.129	N	0.259	neutral	None	None	None	None	I
T/W	0.6371	likely_pathogenic	0.5995	pathogenic	-0.975	Destabilizing	0.983	D	0.336	neutral	None	None	None	None	I
T/Y	0.297	likely_benign	0.2744	benign	-0.655	Destabilizing	0.01	N	0.281	neutral	None	None	None	None	I

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.