TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22496	67711;67712;67713	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
N2AB	20855	62788;62789;62790	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
N2A	19928	60007;60008;60009	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
N2B	13431	40516;40517;40518	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
Novex-1	13556	40891;40892;40893	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
Novex-2	13623	41092;41093;41094	chr2:178579711;178579710;178579709	chr2:179444438;179444437;179444436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-51
• Domain position: 46
• Structural Position: 64
• Q(SASA): 0.5696
• 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/R	rs397517669	-0.205	0.955	N	0.497	0.206	0.231873229951	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.57E-05	0
K/R	rs397517669	-0.205	0.955	N	0.497	0.206	0.231873229951	gnomAD-4.0.0	1.43722E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-05	0	1.65739E-05

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	0.318	likely_benign	0.2915	benign	-0.157	Destabilizing	0.983	D	0.521	neutral	None	None	None	None	N
K/C	0.5889	likely_pathogenic	0.5489	ambiguous	-0.203	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.5107	ambiguous	0.4941	ambiguous	0.092	Stabilizing	0.995	D	0.541	neutral	None	None	None	None	N
K/E	0.1616	likely_benign	0.1578	benign	0.132	Stabilizing	0.955	D	0.517	neutral	N	0.467415263	None	None	N
K/F	0.7457	likely_pathogenic	0.7468	pathogenic	-0.156	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/G	0.4002	ambiguous	0.3781	ambiguous	-0.428	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
K/H	0.2735	likely_benign	0.252	benign	-0.767	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
K/I	0.2823	likely_benign	0.2868	benign	0.496	Stabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
K/L	0.345	ambiguous	0.3389	benign	0.496	Stabilizing	0.995	D	0.529	neutral	None	None	None	None	N
K/M	0.2379	likely_benign	0.2358	benign	0.331	Stabilizing	0.999	D	0.587	neutral	N	0.473877227	None	None	N
K/N	0.3392	likely_benign	0.331	benign	0.075	Stabilizing	0.993	D	0.554	neutral	N	0.504512214	None	None	N
K/P	0.8655	likely_pathogenic	0.8747	pathogenic	0.309	Stabilizing	0.998	D	0.557	neutral	None	None	None	None	N
K/Q	0.1163	likely_benign	0.1098	benign	-0.072	Destabilizing	0.568	D	0.41	neutral	N	0.492852425	None	None	N
K/R	0.0853	likely_benign	0.0812	benign	-0.242	Destabilizing	0.955	D	0.497	neutral	N	0.467706052	None	None	N
K/S	0.3458	ambiguous	0.328	benign	-0.476	Destabilizing	0.983	D	0.531	neutral	None	None	None	None	N
K/T	0.1444	likely_benign	0.1372	benign	-0.264	Destabilizing	0.993	D	0.553	neutral	N	0.483232865	None	None	N
K/V	0.2604	likely_benign	0.2582	benign	0.309	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	N
K/W	0.7944	likely_pathogenic	0.7765	pathogenic	-0.11	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.5989	likely_pathogenic	0.5879	pathogenic	0.207	Stabilizing	0.999	D	0.63	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.