TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22296	67111;67112;67113	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
N2AB	20655	62188;62189;62190	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
N2A	19728	59407;59408;59409	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
N2B	13231	39916;39917;39918	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
Novex-1	13356	40291;40292;40293	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
Novex-2	13423	40492;40493;40494	chr2:178580493;178580492;178580491	chr2:179445220;179445219;179445218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-126
• Domain position: 32
• Structural Position: 49
• Q(SASA): 0.119
• 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/C	None	None	0.994	N	0.581	0.266	0.259761712551	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43353E-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	0.1029	likely_benign	0.0969	benign	-0.652	Destabilizing	0.012	N	0.239	neutral	N	0.476063671	None	None	N
S/C	0.109	likely_benign	0.1064	benign	-0.335	Destabilizing	0.994	D	0.581	neutral	N	0.464161584	None	None	N
S/D	0.5551	ambiguous	0.4513	ambiguous	0.474	Stabilizing	0.854	D	0.534	neutral	None	None	None	None	N
S/E	0.4553	ambiguous	0.3723	ambiguous	0.545	Stabilizing	0.742	D	0.531	neutral	None	None	None	None	N
S/F	0.2585	likely_benign	0.2145	benign	-0.857	Destabilizing	0.979	D	0.617	neutral	N	0.472943221	None	None	N
S/G	0.1345	likely_benign	0.1203	benign	-0.939	Destabilizing	0.543	D	0.519	neutral	None	None	None	None	N
S/H	0.289	likely_benign	0.2591	benign	-1.166	Destabilizing	0.953	D	0.593	neutral	None	None	None	None	N
S/I	0.2035	likely_benign	0.1652	benign	0.022	Stabilizing	0.91	D	0.611	neutral	None	None	None	None	N
S/K	0.5758	likely_pathogenic	0.5158	ambiguous	0.042	Stabilizing	0.59	D	0.515	neutral	None	None	None	None	N
S/L	0.114	likely_benign	0.1121	benign	0.022	Stabilizing	0.742	D	0.558	neutral	None	None	None	None	N
S/M	0.179	likely_benign	0.159	benign	-0.045	Destabilizing	0.984	D	0.595	neutral	None	None	None	None	N
S/N	0.1652	likely_benign	0.1405	benign	-0.196	Destabilizing	0.742	D	0.54	neutral	None	None	None	None	N
S/P	0.9848	likely_pathogenic	0.9794	pathogenic	-0.169	Destabilizing	0.939	D	0.596	neutral	N	0.4752644	None	None	N
S/Q	0.3745	ambiguous	0.3321	benign	-0.13	Destabilizing	0.91	D	0.587	neutral	None	None	None	None	N
S/R	0.5202	ambiguous	0.4419	ambiguous	-0.096	Destabilizing	0.009	N	0.436	neutral	None	None	None	None	N
S/T	0.0804	likely_benign	0.0744	benign	-0.223	Destabilizing	0.012	N	0.226	neutral	N	0.414687138	None	None	N
S/V	0.1958	likely_benign	0.1668	benign	-0.169	Destabilizing	0.742	D	0.571	neutral	None	None	None	None	N
S/W	0.4204	ambiguous	0.3676	ambiguous	-0.877	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
S/Y	0.2176	likely_benign	0.1916	benign	-0.508	Destabilizing	0.979	D	0.625	neutral	N	0.481736063	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.