TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32094	96505;96506;96507	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
N2AB	30453	91582;91583;91584	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
N2A	29526	88801;88802;88803	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
N2B	23029	69310;69311;69312	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
Novex-1	23154	69685;69686;69687	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
Novex-2	23221	69886;69887;69888	chr2:178543864;178543863;178543862	chr2:179408591;179408590;179408589
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-153
• Domain position: 78
• Structural Position: 166
• Q(SASA): 0.2594
• 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
K/N	None	None	1.0	N	0.707	0.427	0.245660935333	gnomAD-4.0.0	6.8426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99526E-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
K/A	0.6325	likely_pathogenic	0.55	ambiguous	0.061	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
K/C	0.8098	likely_pathogenic	0.7464	pathogenic	-0.28	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.9217	likely_pathogenic	0.8863	pathogenic	-0.055	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/E	0.6001	likely_pathogenic	0.4984	ambiguous	-0.065	Destabilizing	0.999	D	0.62	neutral	N	0.521282326	None	None	N
K/F	0.9285	likely_pathogenic	0.8831	pathogenic	-0.238	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/G	0.8353	likely_pathogenic	0.778	pathogenic	-0.095	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/H	0.5629	ambiguous	0.4864	ambiguous	-0.286	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/I	0.5753	likely_pathogenic	0.4769	ambiguous	0.385	Stabilizing	1.0	D	0.769	deleterious	N	0.481534646	None	None	N
K/L	0.649	likely_pathogenic	0.557	ambiguous	0.385	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/M	0.45	ambiguous	0.3592	ambiguous	0.128	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/N	0.7883	likely_pathogenic	0.717	pathogenic	0.194	Stabilizing	1.0	D	0.707	prob.neutral	N	0.495594285	None	None	N
K/P	0.991	likely_pathogenic	0.9859	pathogenic	0.303	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/Q	0.2597	likely_benign	0.2188	benign	0.018	Stabilizing	1.0	D	0.711	prob.delet.	D	0.527997654	None	None	N
K/R	0.1198	likely_benign	0.1081	benign	-0.005	Destabilizing	0.999	D	0.572	neutral	N	0.488099093	None	None	N
K/S	0.7664	likely_pathogenic	0.6921	pathogenic	-0.239	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
K/T	0.4299	ambiguous	0.3553	ambiguous	-0.119	Destabilizing	1.0	D	0.741	deleterious	N	0.519359528	None	None	N
K/V	0.4844	ambiguous	0.3987	ambiguous	0.303	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/W	0.9444	likely_pathogenic	0.9092	pathogenic	-0.295	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Y	0.8369	likely_pathogenic	0.768	pathogenic	0.068	Stabilizing	1.0	D	0.734	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.