TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5814	17665;17666;17667	chr2:178731326;178731325;178731324	chr2:179596053;179596052;179596051
N2AB	5497	16714;16715;16716	chr2:178731326;178731325;178731324	chr2:179596053;179596052;179596051
N2A	4570	13933;13934;13935	chr2:178731326;178731325;178731324	chr2:179596053;179596052;179596051
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-41
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.2985
• 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/F	rs1318339227	-0.57	None	N	0.463	0.211	0.482500522706	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/F	rs1318339227	-0.57	None	N	0.463	0.211	0.482500522706	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	0	None	0	0	0	0	0
S/P	None	None	0.741	N	0.566	0.525	0.419335720491	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0959	likely_benign	0.0979	benign	-0.513	Destabilizing	0.052	N	0.525	neutral	N	0.503925623	None	None	N
S/C	0.1765	likely_benign	0.1715	benign	-0.398	Destabilizing	0.915	D	0.546	neutral	N	0.517816824	None	None	N
S/D	0.6619	likely_pathogenic	0.5478	ambiguous	-0.104	Destabilizing	0.081	N	0.509	neutral	None	None	None	None	N
S/E	0.7183	likely_pathogenic	0.5966	pathogenic	-0.143	Destabilizing	0.002	N	0.413	neutral	None	None	None	None	N
S/F	0.1459	likely_benign	0.1348	benign	-0.753	Destabilizing	None	N	0.463	neutral	N	0.519631674	None	None	N
S/G	0.1582	likely_benign	0.1559	benign	-0.727	Destabilizing	0.262	N	0.525	neutral	None	None	None	None	N
S/H	0.4288	ambiguous	0.3641	ambiguous	-1.228	Destabilizing	0.555	D	0.553	neutral	None	None	None	None	N
S/I	0.2108	likely_benign	0.1986	benign	-0.063	Destabilizing	0.235	N	0.639	neutral	None	None	None	None	N
S/K	0.8643	likely_pathogenic	0.7776	pathogenic	-0.759	Destabilizing	0.149	N	0.509	neutral	None	None	None	None	N
S/L	0.122	likely_benign	0.1161	benign	-0.063	Destabilizing	0.081	N	0.594	neutral	None	None	None	None	N
S/M	0.2218	likely_benign	0.2142	benign	0.144	Stabilizing	0.555	D	0.553	neutral	None	None	None	None	N
S/N	0.2119	likely_benign	0.1859	benign	-0.574	Destabilizing	0.262	N	0.549	neutral	None	None	None	None	N
S/P	0.619	likely_pathogenic	0.5705	pathogenic	-0.179	Destabilizing	0.741	D	0.566	neutral	N	0.499370174	None	None	N
S/Q	0.6231	likely_pathogenic	0.5604	ambiguous	-0.755	Destabilizing	0.38	N	0.504	neutral	None	None	None	None	N
S/R	0.7983	likely_pathogenic	0.6945	pathogenic	-0.598	Destabilizing	0.38	N	0.565	neutral	None	None	None	None	N
S/T	0.094	likely_benign	0.0883	benign	-0.614	Destabilizing	0.002	N	0.426	neutral	N	0.479590419	None	None	N
S/V	0.1895	likely_benign	0.1803	benign	-0.179	Destabilizing	0.081	N	0.599	neutral	None	None	None	None	N
S/W	0.3588	ambiguous	0.3235	benign	-0.749	Destabilizing	0.824	D	0.671	neutral	None	None	None	None	N
S/Y	0.174	likely_benign	0.1576	benign	-0.495	Destabilizing	0.188	N	0.639	neutral	D	0.528347158	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.