TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7609	23050;23051;23052	chr2:178721194;178721193;178721192	chr2:179585921;179585920;179585919
N2AB	7292	22099;22100;22101	chr2:178721194;178721193;178721192	chr2:179585921;179585920;179585919
N2A	6365	19318;19319;19320	chr2:178721194;178721193;178721192	chr2:179585921;179585920;179585919
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-61
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6639
• 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/N	None	None	0.997	D	0.454	0.301	0.408036853922	gnomAD-4.0.0	6.93103E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.18601E-05	0
K/R	None	None	0.98	N	0.422	0.196	0.568250393081	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.3711	ambiguous	0.357	ambiguous	-0.095	Destabilizing	0.985	D	0.462	neutral	None	None	None	None	N
K/C	0.732	likely_pathogenic	0.7369	pathogenic	-0.395	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/D	0.7776	likely_pathogenic	0.7745	pathogenic	0.171	Stabilizing	0.971	D	0.463	neutral	None	None	None	None	N
K/E	0.2975	likely_benign	0.2848	benign	0.218	Stabilizing	0.4	N	0.255	neutral	N	0.473568523	None	None	N
K/F	0.7655	likely_pathogenic	0.7807	pathogenic	-0.164	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
K/G	0.5553	ambiguous	0.5527	ambiguous	-0.333	Destabilizing	0.998	D	0.464	neutral	None	None	None	None	N
K/H	0.2838	likely_benign	0.307	benign	-0.488	Destabilizing	1.0	D	0.518	neutral	None	None	None	None	N
K/I	0.3381	likely_benign	0.3401	ambiguous	0.464	Stabilizing	0.671	D	0.431	neutral	None	None	None	None	N
K/L	0.3815	ambiguous	0.3847	ambiguous	0.464	Stabilizing	0.971	D	0.449	neutral	None	None	None	None	N
K/M	0.2826	likely_benign	0.2763	benign	0.067	Stabilizing	0.999	D	0.521	neutral	D	0.532483541	None	None	N
K/N	0.5461	ambiguous	0.5427	ambiguous	0.013	Stabilizing	0.997	D	0.454	neutral	D	0.531963466	None	None	N
K/P	0.9545	likely_pathogenic	0.9491	pathogenic	0.307	Stabilizing	0.999	D	0.514	neutral	None	None	None	None	N
K/Q	0.1361	likely_benign	0.1403	benign	-0.06	Destabilizing	0.994	D	0.478	neutral	N	0.476686186	None	None	N
K/R	0.0727	likely_benign	0.0728	benign	-0.092	Destabilizing	0.98	D	0.422	neutral	N	0.464122321	None	None	N
K/S	0.4323	ambiguous	0.4423	ambiguous	-0.502	Destabilizing	0.985	D	0.429	neutral	None	None	None	None	N
K/T	0.1663	likely_benign	0.1691	benign	-0.285	Destabilizing	0.997	D	0.459	neutral	N	0.448750224	None	None	N
K/V	0.2819	likely_benign	0.2741	benign	0.307	Stabilizing	0.971	D	0.448	neutral	None	None	None	None	N
K/W	0.7725	likely_pathogenic	0.8033	pathogenic	-0.179	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
K/Y	0.6464	likely_pathogenic	0.6695	pathogenic	0.162	Stabilizing	0.999	D	0.604	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.