TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23406	70441;70442;70443	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
N2AB	21765	65518;65519;65520	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
N2A	20838	62737;62738;62739	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
N2B	14341	43246;43247;43248	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
Novex-1	14466	43621;43622;43623	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
Novex-2	14533	43822;43823;43824	chr2:178575916;178575915;178575914	chr2:179440643;179440642;179440641
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-129
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.356
• 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
N/K	rs757600380	0.15	0.684	N	0.298	0.173	0.210429274316	gnomAD-4.0.0	1.59168E-06	None	None	None	None	I	None	0	0	None	0	2.77377E-05	None	0	0	0	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
N/A	0.5314	ambiguous	0.6262	pathogenic	-0.864	Destabilizing	0.373	N	0.422	neutral	None	None	None	None	I
N/C	0.4187	ambiguous	0.4756	ambiguous	0.121	Stabilizing	0.996	D	0.473	neutral	None	None	None	None	I
N/D	0.139	likely_benign	0.1871	benign	-0.525	Destabilizing	0.684	D	0.344	neutral	N	0.488132544	None	None	I
N/E	0.7114	likely_pathogenic	0.788	pathogenic	-0.476	Destabilizing	0.742	D	0.305	neutral	None	None	None	None	I
N/F	0.8338	likely_pathogenic	0.8804	pathogenic	-0.854	Destabilizing	0.953	D	0.49	neutral	None	None	None	None	I
N/G	0.4014	ambiguous	0.4876	ambiguous	-1.158	Destabilizing	0.373	N	0.334	neutral	None	None	None	None	I
N/H	0.199	likely_benign	0.2192	benign	-1.059	Destabilizing	0.979	D	0.411	neutral	N	0.511702837	None	None	I
N/I	0.6423	likely_pathogenic	0.7222	pathogenic	-0.134	Destabilizing	0.884	D	0.469	neutral	N	0.520861038	None	None	I
N/K	0.651	likely_pathogenic	0.761	pathogenic	-0.262	Destabilizing	0.684	D	0.298	neutral	N	0.470853505	None	None	I
N/L	0.4772	ambiguous	0.5527	ambiguous	-0.134	Destabilizing	0.59	D	0.465	neutral	None	None	None	None	I
N/M	0.5822	likely_pathogenic	0.6698	pathogenic	0.482	Stabilizing	0.996	D	0.449	neutral	None	None	None	None	I
N/P	0.9248	likely_pathogenic	0.9442	pathogenic	-0.348	Destabilizing	0.953	D	0.449	neutral	None	None	None	None	I
N/Q	0.6389	likely_pathogenic	0.698	pathogenic	-0.887	Destabilizing	0.91	D	0.38	neutral	None	None	None	None	I
N/R	0.6944	likely_pathogenic	0.7832	pathogenic	-0.234	Destabilizing	0.742	D	0.375	neutral	None	None	None	None	I
N/S	0.0956	likely_benign	0.1096	benign	-0.768	Destabilizing	0.028	N	0.187	neutral	N	0.486343033	None	None	I
N/T	0.124	likely_benign	0.1629	benign	-0.537	Destabilizing	0.004	N	0.139	neutral	N	0.447112641	None	None	I
N/V	0.566	likely_pathogenic	0.6506	pathogenic	-0.348	Destabilizing	0.59	D	0.451	neutral	None	None	None	None	I
N/W	0.9531	likely_pathogenic	0.9655	pathogenic	-0.657	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	I
N/Y	0.5113	ambiguous	0.5792	pathogenic	-0.454	Destabilizing	0.979	D	0.465	neutral	N	0.500140188	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.