TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22637	68134;68135;68136	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
N2AB	20996	63211;63212;63213	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
N2A	20069	60430;60431;60432	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
N2B	13572	40939;40940;40941	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
Novex-1	13697	41314;41315;41316	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
Novex-2	13764	41515;41516;41517	chr2:178579121;178579120;178579119	chr2:179443848;179443847;179443846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-127
• Domain position: 78
• Structural Position: 173
• Q(SASA): 0.5388
• 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
S/C	rs1233992072	-0.117	0.612	N	0.46	0.355	0.547039986869	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/C	rs1233992072	-0.117	0.612	N	0.46	0.355	0.547039986869	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85977E-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	0.0822	likely_benign	0.0811	benign	-0.409	Destabilizing	None	N	0.161	neutral	N	0.503872788	None	None	I
S/C	0.0955	likely_benign	0.1022	benign	-0.368	Destabilizing	0.612	D	0.46	neutral	N	0.495193119	None	None	I
S/D	0.32	likely_benign	0.2943	benign	0.417	Stabilizing	None	N	0.212	neutral	None	None	None	None	I
S/E	0.4407	ambiguous	0.4258	ambiguous	0.395	Stabilizing	0.016	N	0.271	neutral	None	None	None	None	I
S/F	0.1141	likely_benign	0.1131	benign	-0.737	Destabilizing	None	N	0.235	neutral	N	0.450155733	None	None	I
S/G	0.1174	likely_benign	0.1141	benign	-0.616	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	I
S/H	0.2319	likely_benign	0.2379	benign	-1.03	Destabilizing	0.356	N	0.476	neutral	None	None	None	None	I
S/I	0.1225	likely_benign	0.1216	benign	0.019	Stabilizing	0.038	N	0.511	neutral	None	None	None	None	I
S/K	0.6136	likely_pathogenic	0.5963	pathogenic	-0.39	Destabilizing	0.038	N	0.237	neutral	None	None	None	None	I
S/L	0.0929	likely_benign	0.0907	benign	0.019	Stabilizing	0.016	N	0.479	neutral	None	None	None	None	I
S/M	0.1487	likely_benign	0.1433	benign	-0.004	Destabilizing	0.356	N	0.475	neutral	None	None	None	None	I
S/N	0.1091	likely_benign	0.0997	benign	-0.32	Destabilizing	0.072	N	0.292	neutral	None	None	None	None	I
S/P	0.5766	likely_pathogenic	0.5747	pathogenic	-0.09	Destabilizing	0.106	N	0.483	neutral	D	0.534542411	None	None	I
S/Q	0.4017	ambiguous	0.3901	ambiguous	-0.405	Destabilizing	0.003	N	0.238	neutral	None	None	None	None	I
S/R	0.5094	ambiguous	0.5065	ambiguous	-0.332	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	I
S/T	0.0646	likely_benign	0.0604	benign	-0.366	Destabilizing	None	N	0.164	neutral	N	0.456598916	None	None	I
S/V	0.1339	likely_benign	0.1329	benign	-0.09	Destabilizing	0.038	N	0.493	neutral	None	None	None	None	I
S/W	0.224	likely_benign	0.2373	benign	-0.77	Destabilizing	0.864	D	0.483	neutral	None	None	None	None	I
S/Y	0.1214	likely_benign	0.1247	benign	-0.458	Destabilizing	0.093	N	0.471	neutral	N	0.509761397	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.