TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7707	23344;23345;23346	chr2:178720643;178720642;178720641	chr2:179585370;179585369;179585368
N2AB	7390	22393;22394;22395	chr2:178720643;178720642;178720641	chr2:179585370;179585369;179585368
N2A	6463	19612;19613;19614	chr2:178720643;178720642;178720641	chr2:179585370;179585369;179585368
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-62
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7487
• 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/R	None	None	0.144	N	0.329	0.139	0.242825505644	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.3052	likely_benign	0.3128	benign	-0.514	Destabilizing	0.007	N	0.161	neutral	None	None	None	None	N
K/C	0.6584	likely_pathogenic	0.675	pathogenic	-0.462	Destabilizing	0.99	D	0.295	neutral	None	None	None	None	N
K/D	0.6557	likely_pathogenic	0.6291	pathogenic	0.196	Stabilizing	0.376	N	0.375	neutral	None	None	None	None	N
K/E	0.1953	likely_benign	0.1893	benign	0.285	Stabilizing	0.004	N	0.168	neutral	N	0.466007833	None	None	N
K/F	0.5899	likely_pathogenic	0.5904	pathogenic	-0.311	Destabilizing	0.773	D	0.334	neutral	None	None	None	None	N
K/G	0.4699	ambiguous	0.4715	ambiguous	-0.843	Destabilizing	0.547	D	0.387	neutral	None	None	None	None	N
K/H	0.3084	likely_benign	0.3136	benign	-1.165	Destabilizing	0.781	D	0.323	neutral	None	None	None	None	N
K/I	0.208	likely_benign	0.1988	benign	0.32	Stabilizing	0.017	N	0.412	neutral	None	None	None	None	N
K/L	0.2499	likely_benign	0.2428	benign	0.32	Stabilizing	0.007	N	0.363	neutral	None	None	None	None	N
K/M	0.1492	likely_benign	0.1488	benign	0.151	Stabilizing	0.436	N	0.323	neutral	N	0.512043153	None	None	N
K/N	0.3899	ambiguous	0.3653	ambiguous	-0.159	Destabilizing	0.648	D	0.285	neutral	D	0.525229495	None	None	N
K/P	0.4826	ambiguous	0.4784	ambiguous	0.072	Stabilizing	0.004	N	0.212	neutral	None	None	None	None	N
K/Q	0.1233	likely_benign	0.1259	benign	-0.249	Destabilizing	0.004	N	0.186	neutral	N	0.50631566	None	None	N
K/R	0.0938	likely_benign	0.0977	benign	-0.397	Destabilizing	0.144	N	0.329	neutral	N	0.478649056	None	None	N
K/S	0.3768	ambiguous	0.3767	ambiguous	-0.834	Destabilizing	0.199	N	0.268	neutral	None	None	None	None	N
K/T	0.1511	likely_benign	0.1581	benign	-0.544	Destabilizing	0.215	N	0.371	neutral	N	0.467874702	None	None	N
K/V	0.2312	likely_benign	0.2265	benign	0.072	Stabilizing	None	N	0.175	neutral	None	None	None	None	N
K/W	0.7074	likely_pathogenic	0.7249	pathogenic	-0.178	Destabilizing	0.993	D	0.307	neutral	None	None	None	None	N
K/Y	0.4729	ambiguous	0.4737	ambiguous	0.109	Stabilizing	0.549	D	0.339	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.