TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17750	53473;53474;53475	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
N2AB	16109	48550;48551;48552	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
N2A	15182	45769;45770;45771	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
N2B	8685	26278;26279;26280	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
Novex-1	8810	26653;26654;26655	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
Novex-2	8877	26854;26855;26856	chr2:178607440;178607439;178607438	chr2:179472167;179472166;179472165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-113
• Domain position: 74
• Structural Position: 163
• Q(SASA): 0.7888
• 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
C/Y	rs1666217095	None	0.921	N	0.579	0.266	0.548822617668	gnomAD-4.0.0	4.79106E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29807E-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
C/A	0.3163	likely_benign	0.2818	benign	-0.417	Destabilizing	0.027	N	0.288	neutral	None	None	None	None	I
C/D	0.8294	likely_pathogenic	0.7925	pathogenic	0.186	Stabilizing	0.228	N	0.565	neutral	None	None	None	None	I
C/E	0.8683	likely_pathogenic	0.8472	pathogenic	0.125	Stabilizing	0.228	N	0.561	neutral	None	None	None	None	I
C/F	0.2552	likely_benign	0.2323	benign	-0.676	Destabilizing	0.794	D	0.575	neutral	N	0.362493889	None	None	I
C/G	0.2218	likely_benign	0.1988	benign	-0.457	Destabilizing	0.047	N	0.613	neutral	N	0.41805917	None	None	I
C/H	0.5138	ambiguous	0.4852	ambiguous	-0.354	Destabilizing	0.836	D	0.555	neutral	None	None	None	None	I
C/I	0.6332	likely_pathogenic	0.5765	pathogenic	-0.399	Destabilizing	0.593	D	0.487	neutral	None	None	None	None	I
C/K	0.8739	likely_pathogenic	0.852	pathogenic	0.065	Stabilizing	0.129	N	0.569	neutral	None	None	None	None	I
C/L	0.5309	ambiguous	0.5139	ambiguous	-0.399	Destabilizing	0.228	N	0.549	neutral	None	None	None	None	I
C/M	0.6497	likely_pathogenic	0.6272	pathogenic	-0.175	Destabilizing	0.94	D	0.504	neutral	None	None	None	None	I
C/N	0.5276	ambiguous	0.5163	ambiguous	0.364	Stabilizing	0.129	N	0.555	neutral	None	None	None	None	I
C/P	0.9755	likely_pathogenic	0.9716	pathogenic	-0.388	Destabilizing	0.593	D	0.563	neutral	None	None	None	None	I
C/Q	0.703	likely_pathogenic	0.667	pathogenic	0.189	Stabilizing	0.418	N	0.551	neutral	None	None	None	None	I
C/R	0.6081	likely_pathogenic	0.5531	ambiguous	0.364	Stabilizing	0.351	N	0.561	neutral	N	0.448728794	None	None	I
C/S	0.1819	likely_benign	0.1618	benign	-0.005	Destabilizing	0.001	N	0.353	neutral	N	0.360339018	None	None	I
C/T	0.4228	ambiguous	0.369	ambiguous	0.016	Stabilizing	0.061	N	0.523	neutral	None	None	None	None	I
C/V	0.465	ambiguous	0.4203	ambiguous	-0.388	Destabilizing	0.228	N	0.503	neutral	None	None	None	None	I
C/W	0.601	likely_pathogenic	0.5529	ambiguous	-0.678	Destabilizing	0.978	D	0.574	neutral	N	0.46793063	None	None	I
C/Y	0.384	ambiguous	0.3588	ambiguous	-0.485	Destabilizing	0.921	D	0.579	neutral	N	0.393528872	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.