TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35433	106522;106523;106524	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
N2AB	33792	101599;101600;101601	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
N2A	32865	98818;98819;98820	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
N2B	26368	79327;79328;79329	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
Novex-1	26493	79702;79703;79704	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
Novex-2	26560	79903;79904;79905	chr2:178530318;178530317;178530316	chr2:179395045;179395044;179395043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-166
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.1675
• 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
S/L	None	None	0.085	N	0.391	0.115	0.278143212241	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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
S/A	0.0684	likely_benign	0.0677	benign	-0.507	Destabilizing	None	N	0.131	neutral	N	0.385729668	None	None	N
S/C	0.1962	likely_benign	0.2021	benign	-0.2	Destabilizing	0.869	D	0.325	neutral	None	None	None	None	N
S/D	0.3532	ambiguous	0.3475	ambiguous	-0.067	Destabilizing	0.198	N	0.365	neutral	None	None	None	None	N
S/E	0.3931	ambiguous	0.3677	ambiguous	-0.169	Destabilizing	0.198	N	0.317	neutral	None	None	None	None	N
S/F	0.1895	likely_benign	0.1927	benign	-1.208	Destabilizing	0.637	D	0.452	neutral	None	None	None	None	N
S/G	0.1007	likely_benign	0.1005	benign	-0.588	Destabilizing	0.049	N	0.34	neutral	None	None	None	None	N
S/H	0.3795	ambiguous	0.3711	ambiguous	-1.189	Destabilizing	0.953	D	0.323	neutral	None	None	None	None	N
S/I	0.1748	likely_benign	0.1649	benign	-0.415	Destabilizing	0.464	N	0.453	neutral	None	None	None	None	N
S/K	0.5088	ambiguous	0.4798	ambiguous	-0.371	Destabilizing	0.198	N	0.314	neutral	None	None	None	None	N
S/L	0.0961	likely_benign	0.0946	benign	-0.415	Destabilizing	0.085	N	0.391	neutral	N	0.399891044	None	None	N
S/M	0.2186	likely_benign	0.2259	benign	0.091	Stabilizing	0.637	D	0.329	neutral	None	None	None	None	N
S/N	0.175	likely_benign	0.1695	benign	-0.087	Destabilizing	0.198	N	0.447	neutral	None	None	None	None	N
S/P	0.1574	likely_benign	0.1344	benign	-0.421	Destabilizing	0.57	D	0.351	neutral	N	0.451570658	None	None	N
S/Q	0.4433	ambiguous	0.4236	ambiguous	-0.441	Destabilizing	0.637	D	0.354	neutral	None	None	None	None	N
S/R	0.4419	ambiguous	0.4058	ambiguous	-0.144	Destabilizing	0.464	N	0.347	neutral	None	None	None	None	N
S/T	0.0832	likely_benign	0.0852	benign	-0.217	Destabilizing	0.002	N	0.172	neutral	N	0.449954505	None	None	N
S/V	0.1713	likely_benign	0.168	benign	-0.421	Destabilizing	0.11	N	0.41	neutral	None	None	None	None	N
S/W	0.3215	likely_benign	0.3259	benign	-1.172	Destabilizing	0.953	D	0.569	neutral	None	None	None	None	N
S/Y	0.1844	likely_benign	0.1867	benign	-0.894	Destabilizing	0.842	D	0.445	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.