TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28787	86584;86585;86586	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
N2AB	27146	81661;81662;81663	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
N2A	26219	78880;78881;78882	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
N2B	19722	59389;59390;59391	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
Novex-1	19847	59764;59765;59766	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
Novex-2	19914	59965;59966;59967	chr2:178559773;178559772;178559771	chr2:179424500;179424499;179424498
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-144
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.5756
• 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
L/S	rs1237283720	-1.053	None	N	0.256	0.105	0.181679512989	gnomAD-2.1.1	4.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.13E-06	0
L/S	rs1237283720	-1.053	None	N	0.256	0.105	0.181679512989	gnomAD-4.0.0	1.61777E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89942E-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
L/A	0.0939	likely_benign	0.0931	benign	-0.896	Destabilizing	None	N	0.193	neutral	None	None	None	None	N
L/C	0.2469	likely_benign	0.2463	benign	-0.791	Destabilizing	0.245	N	0.449	neutral	None	None	None	None	N
L/D	0.3859	ambiguous	0.3616	ambiguous	-0.147	Destabilizing	0.009	N	0.477	neutral	None	None	None	None	N
L/E	0.2106	likely_benign	0.1943	benign	-0.179	Destabilizing	0.009	N	0.421	neutral	None	None	None	None	N
L/F	0.0776	likely_benign	0.0744	benign	-0.61	Destabilizing	0.033	N	0.36	neutral	N	0.441880179	None	None	N
L/G	0.2853	likely_benign	0.2777	benign	-1.134	Destabilizing	0.009	N	0.4	neutral	None	None	None	None	N
L/H	0.1044	likely_benign	0.1016	benign	-0.256	Destabilizing	0.245	N	0.498	neutral	None	None	None	None	N
L/I	0.0607	likely_benign	0.0596	benign	-0.359	Destabilizing	None	N	0.15	neutral	None	None	None	None	N
L/K	0.1786	likely_benign	0.1692	benign	-0.522	Destabilizing	0.009	N	0.409	neutral	None	None	None	None	N
L/M	0.0639	likely_benign	0.0636	benign	-0.506	Destabilizing	None	N	0.147	neutral	N	0.436858362	None	None	N
L/N	0.1427	likely_benign	0.1426	benign	-0.431	Destabilizing	0.022	N	0.513	neutral	None	None	None	None	N
L/P	0.8807	likely_pathogenic	0.8733	pathogenic	-0.505	Destabilizing	0.044	N	0.551	neutral	None	None	None	None	N
L/Q	0.082	likely_benign	0.0797	benign	-0.566	Destabilizing	0.001	N	0.29	neutral	None	None	None	None	N
L/R	0.1433	likely_benign	0.1331	benign	-0.007	Destabilizing	0.022	N	0.512	neutral	None	None	None	None	N
L/S	0.0786	likely_benign	0.0792	benign	-0.983	Destabilizing	None	N	0.256	neutral	N	0.402105496	None	None	N
L/T	0.0669	likely_benign	0.0688	benign	-0.892	Destabilizing	None	N	0.195	neutral	None	None	None	None	N
L/V	0.0618	likely_benign	0.0604	benign	-0.505	Destabilizing	None	N	0.119	neutral	N	0.409594403	None	None	N
L/W	0.1713	likely_benign	0.1623	benign	-0.642	Destabilizing	0.737	D	0.501	neutral	N	0.485150954	None	None	N
L/Y	0.185	likely_benign	0.1755	benign	-0.403	Destabilizing	0.085	N	0.495	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.