TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8737	26434;26435;26436	chr2:178714565;178714564;178714563	chr2:179579292;179579291;179579290
N2AB	8420	25483;25484;25485	chr2:178714565;178714564;178714563	chr2:179579292;179579291;179579290
N2A	7493	22702;22703;22704	chr2:178714565;178714564;178714563	chr2:179579292;179579291;179579290
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-73
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4902
• 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
R/K	rs769711887	-0.113	None	N	0.092	0.159	0.225902525712	gnomAD-2.1.1	4.19E-06	None	None	None	None	N	None	0	0	None	0	5.7E-05	None	0	None	0	0	0
R/K	rs769711887	-0.113	None	N	0.092	0.159	0.225902525712	gnomAD-4.0.0	6.9355E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08698E-07	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
R/A	0.1678	likely_benign	0.2182	benign	-0.304	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
R/C	0.1017	likely_benign	0.1361	benign	-0.498	Destabilizing	0.141	N	0.273	neutral	None	None	None	None	N
R/D	0.4291	ambiguous	0.5804	pathogenic	-0.046	Destabilizing	0.009	N	0.27	neutral	None	None	None	None	N
R/E	0.2312	likely_benign	0.3007	benign	0.083	Stabilizing	0.001	N	0.153	neutral	None	None	None	None	N
R/F	0.239	likely_benign	0.319	benign	-0.2	Destabilizing	0.009	N	0.399	neutral	None	None	None	None	N
R/G	0.1282	likely_benign	0.2124	benign	-0.588	Destabilizing	0.002	N	0.235	neutral	N	0.511825662	None	None	N
R/H	0.0702	likely_benign	0.0781	benign	-1.001	Destabilizing	0.033	N	0.265	neutral	None	None	None	None	N
R/I	0.1133	likely_benign	0.1304	benign	0.443	Stabilizing	0.001	N	0.337	neutral	N	0.491759624	None	None	N
R/K	0.0802	likely_benign	0.0854	benign	-0.336	Destabilizing	None	N	0.092	neutral	N	0.509006462	None	None	N
R/L	0.1132	likely_benign	0.1362	benign	0.443	Stabilizing	None	N	0.189	neutral	None	None	None	None	N
R/M	0.1355	likely_benign	0.1617	benign	-0.163	Destabilizing	0.033	N	0.297	neutral	None	None	None	None	N
R/N	0.2614	likely_benign	0.3378	benign	-0.186	Destabilizing	0.005	N	0.203	neutral	None	None	None	None	N
R/P	0.7079	likely_pathogenic	0.8479	pathogenic	0.216	Stabilizing	0.023	N	0.332	neutral	None	None	None	None	N
R/Q	0.0796	likely_benign	0.0874	benign	-0.196	Destabilizing	None	N	0.135	neutral	None	None	None	None	N
R/S	0.1731	likely_benign	0.2505	benign	-0.689	Destabilizing	None	N	0.13	neutral	N	0.463986248	None	None	N
R/T	0.104	likely_benign	0.1261	benign	-0.38	Destabilizing	None	N	0.159	neutral	N	0.483361443	None	None	N
R/V	0.1483	likely_benign	0.1648	benign	0.216	Stabilizing	0.001	N	0.237	neutral	None	None	None	None	N
R/W	0.1162	likely_benign	0.1546	benign	-0.08	Destabilizing	0.738	D	0.266	neutral	None	None	None	None	N
R/Y	0.1869	likely_benign	0.2521	benign	0.264	Stabilizing	0.018	N	0.391	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.