TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23528	70807;70808;70809	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
N2AB	21887	65884;65885;65886	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
N2A	20960	63103;63104;63105	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
N2B	14463	43612;43613;43614	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
Novex-1	14588	43987;43988;43989	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
Novex-2	14655	44188;44189;44190	chr2:178575550;178575549;178575548	chr2:179440277;179440276;179440275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-58
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.5613
• 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/N	None	None	0.163	N	0.628	0.1	0.117506650769	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-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	0.5588	ambiguous	0.5984	pathogenic	-0.165	Destabilizing	0.205	N	0.652	prob.neutral	None	None	None	None	N
K/C	0.6354	likely_pathogenic	0.6492	pathogenic	-0.327	Destabilizing	0.955	D	0.837	deleterious	None	None	None	None	N
K/D	0.9195	likely_pathogenic	0.9431	pathogenic	0.239	Stabilizing	0.475	N	0.643	neutral	None	None	None	None	N
K/E	0.485	ambiguous	0.5377	ambiguous	0.265	Stabilizing	0.028	N	0.601	neutral	N	0.464969094	None	None	N
K/F	0.7824	likely_pathogenic	0.8258	pathogenic	-0.284	Destabilizing	0.422	N	0.827	deleterious	None	None	None	None	N
K/G	0.7556	likely_pathogenic	0.7976	pathogenic	-0.403	Destabilizing	0.205	N	0.676	prob.neutral	None	None	None	None	N
K/H	0.3808	ambiguous	0.4005	ambiguous	-0.695	Destabilizing	0.432	N	0.739	deleterious	None	None	None	None	N
K/I	0.3319	likely_benign	0.3879	ambiguous	0.389	Stabilizing	0.039	N	0.817	deleterious	N	0.503757279	None	None	N
K/L	0.3313	likely_benign	0.3973	ambiguous	0.389	Stabilizing	0.008	N	0.676	prob.neutral	None	None	None	None	N
K/M	0.2934	likely_benign	0.3371	benign	0.253	Stabilizing	0.716	D	0.737	deleterious	None	None	None	None	N
K/N	0.772	likely_pathogenic	0.8139	pathogenic	0.134	Stabilizing	0.163	N	0.628	neutral	N	0.471641365	None	None	N
K/P	0.8254	likely_pathogenic	0.854	pathogenic	0.234	Stabilizing	0.647	D	0.715	prob.delet.	None	None	None	None	N
K/Q	0.2078	likely_benign	0.2169	benign	-0.056	Destabilizing	0.023	N	0.658	prob.neutral	N	0.515051708	None	None	N
K/R	0.0652	likely_benign	0.0669	benign	-0.086	Destabilizing	None	N	0.133	neutral	N	0.457062197	None	None	N
K/S	0.7452	likely_pathogenic	0.7868	pathogenic	-0.475	Destabilizing	0.205	N	0.555	neutral	None	None	None	None	N
K/T	0.3243	likely_benign	0.3516	ambiguous	-0.282	Destabilizing	0.055	N	0.713	prob.delet.	N	0.451159653	None	None	N
K/V	0.3302	likely_benign	0.3901	ambiguous	0.234	Stabilizing	0.034	N	0.614	neutral	None	None	None	None	N
K/W	0.6916	likely_pathogenic	0.7229	pathogenic	-0.214	Destabilizing	0.969	D	0.819	deleterious	None	None	None	None	N
K/Y	0.6971	likely_pathogenic	0.7355	pathogenic	0.128	Stabilizing	0.079	N	0.85	deleterious	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.