TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5395	16408;16409;16410	chr2:178732993;178732992;178732991	chr2:179597720;179597719;179597718
N2AB	5078	15457;15458;15459	chr2:178732993;178732992;178732991	chr2:179597720;179597719;179597718
N2A	4151	12676;12677;12678	chr2:178732993;178732992;178732991	chr2:179597720;179597719;179597718
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-37
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.4772
• 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/E	None	None	0.012	N	0.311	0.24	0.305730143919	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.2075	likely_benign	0.2084	benign	-0.073	Destabilizing	0.016	N	0.354	neutral	None	None	None	None	N
K/C	0.541	ambiguous	0.499	ambiguous	-0.45	Destabilizing	0.864	D	0.316	neutral	None	None	None	None	N
K/D	0.309	likely_benign	0.3206	benign	0.092	Stabilizing	0.038	N	0.361	neutral	None	None	None	None	N
K/E	0.0896	likely_benign	0.0927	benign	0.129	Stabilizing	0.012	N	0.311	neutral	N	0.501600487	None	None	N
K/F	0.5234	ambiguous	0.5071	ambiguous	-0.177	Destabilizing	0.356	N	0.346	neutral	None	None	None	None	N
K/G	0.3089	likely_benign	0.2875	benign	-0.298	Destabilizing	0.016	N	0.379	neutral	None	None	None	None	N
K/H	0.2085	likely_benign	0.2021	benign	-0.46	Destabilizing	0.001	N	0.236	neutral	None	None	None	None	N
K/I	0.1789	likely_benign	0.1788	benign	0.448	Stabilizing	0.029	N	0.412	neutral	N	0.50941468	None	None	N
K/L	0.2056	likely_benign	0.1992	benign	0.448	Stabilizing	0.016	N	0.376	neutral	None	None	None	None	N
K/M	0.135	likely_benign	0.1377	benign	0.045	Stabilizing	0.356	N	0.31	neutral	None	None	None	None	N
K/N	0.1847	likely_benign	0.1905	benign	-0.086	Destabilizing	None	N	0.196	neutral	D	0.534753055	None	None	N
K/P	0.8419	likely_pathogenic	0.8314	pathogenic	0.303	Stabilizing	0.136	N	0.389	neutral	None	None	None	None	N
K/Q	0.0878	likely_benign	0.0863	benign	-0.167	Destabilizing	0.002	N	0.154	neutral	N	0.47045086	None	None	N
K/R	0.0744	likely_benign	0.0704	benign	-0.156	Destabilizing	None	N	0.189	neutral	N	0.503699429	None	None	N
K/S	0.2192	likely_benign	0.223	benign	-0.566	Destabilizing	0.016	N	0.278	neutral	None	None	None	None	N
K/T	0.1111	likely_benign	0.114	benign	-0.367	Destabilizing	0.001	N	0.221	neutral	D	0.53134739	None	None	N
K/V	0.1609	likely_benign	0.1654	benign	0.303	Stabilizing	0.001	N	0.252	neutral	None	None	None	None	N
K/W	0.5955	likely_pathogenic	0.5375	ambiguous	-0.208	Destabilizing	0.864	D	0.334	neutral	None	None	None	None	N
K/Y	0.432	ambiguous	0.4081	ambiguous	0.135	Stabilizing	0.214	N	0.379	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.