TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10137	30634;30635;30636	chr2:178702478;178702477;178702476	chr2:179567205;179567204;179567203
N2AB	9820	29683;29684;29685	chr2:178702478;178702477;178702476	chr2:179567205;179567204;179567203
N2A	8893	26902;26903;26904	chr2:178702478;178702477;178702476	chr2:179567205;179567204;179567203
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-86
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.3791
• 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
H/N	rs2075178264	None	0.811	None	0.35	0.215	0.344945010812	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/N	rs2075178264	None	0.811	None	0.35	0.215	0.344945010812	gnomAD-4.0.0	2.56188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78496E-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
H/A	0.8865	likely_pathogenic	0.9339	pathogenic	-0.54	Destabilizing	0.737	D	0.411	neutral	None	None	None	None	N
H/C	0.7213	likely_pathogenic	0.8095	pathogenic	0.041	Stabilizing	0.998	D	0.478	neutral	None	None	None	None	N
H/D	0.831	likely_pathogenic	0.9084	pathogenic	-0.205	Destabilizing	0.837	D	0.42	neutral	None	None	None	None	N
H/E	0.8621	likely_pathogenic	0.9165	pathogenic	-0.168	Destabilizing	0.584	D	0.265	neutral	None	None	None	None	N
H/F	0.7963	likely_pathogenic	0.8467	pathogenic	-0.129	Destabilizing	0.993	D	0.442	neutral	None	None	None	None	N
H/G	0.9084	likely_pathogenic	0.9474	pathogenic	-0.83	Destabilizing	0.85	D	0.472	neutral	None	None	None	None	N
H/I	0.9338	likely_pathogenic	0.9689	pathogenic	0.217	Stabilizing	0.993	D	0.535	neutral	None	None	None	None	N
H/K	0.777	likely_pathogenic	0.8151	pathogenic	-0.454	Destabilizing	0.037	N	0.116	neutral	None	None	None	None	N
H/L	0.5934	likely_pathogenic	0.7337	pathogenic	0.217	Stabilizing	0.837	D	0.511	neutral	None	None	None	None	N
H/M	0.9294	likely_pathogenic	0.9603	pathogenic	0.198	Stabilizing	0.993	D	0.476	neutral	None	None	None	None	N
H/N	0.4378	ambiguous	0.5811	pathogenic	-0.249	Destabilizing	0.811	D	0.35	neutral	None	None	None	None	N
H/P	0.8751	likely_pathogenic	0.9438	pathogenic	-0.012	Destabilizing	0.969	D	0.507	neutral	None	None	None	None	N
H/Q	0.6617	likely_pathogenic	0.7616	pathogenic	-0.176	Destabilizing	0.166	N	0.115	neutral	None	None	None	None	N
H/R	0.436	ambiguous	0.4862	ambiguous	-0.653	Destabilizing	0.007	N	0.082	neutral	None	None	None	None	N
H/S	0.7522	likely_pathogenic	0.8275	pathogenic	-0.393	Destabilizing	0.737	D	0.409	neutral	None	None	None	None	N
H/T	0.874	likely_pathogenic	0.9227	pathogenic	-0.266	Destabilizing	0.932	D	0.49	neutral	None	None	None	None	N
H/V	0.9089	likely_pathogenic	0.9528	pathogenic	-0.012	Destabilizing	0.932	D	0.535	neutral	None	None	None	None	N
H/W	0.7789	likely_pathogenic	0.8168	pathogenic	-0.039	Destabilizing	0.998	D	0.454	neutral	None	None	None	None	N
H/Y	0.3741	ambiguous	0.4946	ambiguous	0.337	Stabilizing	0.969	D	0.356	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.