TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18880	56863;56864;56865	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
N2AB	17239	51940;51941;51942	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
N2A	16312	49159;49160;49161	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
N2B	9815	29668;29669;29670	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
Novex-1	9940	30043;30044;30045	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
Novex-2	10007	30244;30245;30246	chr2:178599155;178599154;178599153	chr2:179463882;179463881;179463880
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-24
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.9911
• 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
N/K	rs200544272	0.551	0.999	N	0.765	0.252	0.197625483188	gnomAD-2.1.1	6.96E-05	None	None	None	None	N	None	6.13282E-04	0	None	0	0	None	0	None	0	0	0
N/K	rs200544272	0.551	0.999	N	0.765	0.252	0.197625483188	gnomAD-3.1.2	1.05277E-04	None	None	None	None	N	None	3.86529E-04	0	0	0	0	None	0	0	0	0	0
N/K	rs200544272	0.551	0.999	N	0.765	0.252	0.197625483188	gnomAD-4.0.0	1.72725E-05	None	None	None	None	N	None	3.23388E-04	0	None	0	0	None	0	0	8.84305E-07	1.4334E-05	1.73166E-05
N/S	rs1391726501	0.334	0.997	N	0.629	0.262	0.251116650651	gnomAD-2.1.1	5.95E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.91E-05	1.10256E-04	0
N/S	rs1391726501	0.334	0.997	N	0.629	0.262	0.251116650651	gnomAD-3.1.2	6.58E-05	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	1.32407E-04	0	0
N/S	rs1391726501	0.334	0.997	N	0.629	0.262	0.251116650651	gnomAD-4.0.0	2.22597E-05	None	None	None	None	N	None	0	0	None	0	0	None	8.32002E-05	0	2.43424E-05	1.86386E-05	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
N/A	0.7147	likely_pathogenic	0.7447	pathogenic	-0.245	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
N/C	0.6413	likely_pathogenic	0.6666	pathogenic	0.342	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
N/D	0.2312	likely_benign	0.2644	benign	0.148	Stabilizing	0.997	D	0.703	prob.delet.	N	0.460390503	None	None	N
N/E	0.8596	likely_pathogenic	0.8674	pathogenic	0.102	Stabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
N/F	0.8059	likely_pathogenic	0.8451	pathogenic	-0.687	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
N/G	0.7369	likely_pathogenic	0.7423	pathogenic	-0.395	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	N
N/H	0.246	likely_benign	0.2637	benign	-0.442	Destabilizing	0.999	D	0.82	deleterious	N	0.501237048	None	None	N
N/I	0.6152	likely_pathogenic	0.6538	pathogenic	0.055	Stabilizing	0.999	D	0.768	deleterious	N	0.467740571	None	None	N
N/K	0.8481	likely_pathogenic	0.8665	pathogenic	0.152	Stabilizing	0.999	D	0.765	deleterious	N	0.519649451	None	None	N
N/L	0.5402	ambiguous	0.5822	pathogenic	0.055	Stabilizing	0.999	D	0.727	deleterious	None	None	None	None	N
N/M	0.6941	likely_pathogenic	0.7334	pathogenic	0.337	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
N/P	0.7968	likely_pathogenic	0.8103	pathogenic	-0.019	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
N/Q	0.8091	likely_pathogenic	0.8272	pathogenic	-0.279	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
N/R	0.8622	likely_pathogenic	0.877	pathogenic	0.205	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
N/S	0.1932	likely_benign	0.2067	benign	-0.042	Destabilizing	0.997	D	0.629	neutral	N	0.463892168	None	None	N
N/T	0.4902	ambiguous	0.4957	ambiguous	0.047	Stabilizing	0.997	D	0.755	deleterious	N	0.446407194	None	None	N
N/V	0.6527	likely_pathogenic	0.6811	pathogenic	-0.019	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
N/W	0.9271	likely_pathogenic	0.94	pathogenic	-0.711	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
N/Y	0.3459	ambiguous	0.3787	ambiguous	-0.426	Destabilizing	1.0	D	0.787	deleterious	N	0.501237048	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.