TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23248	69967;69968;69969	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
N2AB	21607	65044;65045;65046	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
N2A	20680	62263;62264;62265	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
N2B	14183	42772;42773;42774	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
Novex-1	14308	43147;43148;43149	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
Novex-2	14375	43348;43349;43350	chr2:178576390;178576389;178576388	chr2:179441117;179441116;179441115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-57
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6386
• Predicted PPI site: I

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
H/P	rs1423241119	0.889	0.065	N	0.493	0.109	0.0666544352282	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
H/P	rs1423241119	0.889	0.065	N	0.493	0.109	0.0666544352282	gnomAD-4.0.0	1.91718E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.61655E-05	0	1.72E-06	0	0
H/Q	rs774642251	0.578	0.007	N	0.327	0.114	0.0297737177859	gnomAD-2.1.1	1.48E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.09E-05	0
H/Q	rs774642251	0.578	0.007	N	0.327	0.114	0.0297737177859	gnomAD-4.0.0	2.12342E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.73985E-06	0	0
H/R	None	None	None	N	0.107	0.115	0.0297737177859	gnomAD-4.0.0	7.07834E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.29675E-05	0
H/Y	rs1374089814	1.576	0.065	N	0.449	0.054	0.149567049428	gnomAD-2.1.1	1.7E-05	None	None	None	None	I	None	1.72147E-04	0	None	0	0	None	0	None	0	0	0
H/Y	rs1374089814	1.576	0.065	N	0.449	0.054	0.149567049428	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs1374089814	1.576	0.065	N	0.449	0.054	0.149567049428	gnomAD-4.0.0	6.83062E-06	None	None	None	None	I	None	8.85175E-05	0	None	0	0	None	0	0	0	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
H/A	0.2809	likely_benign	0.2661	benign	-0.317	Destabilizing	0.008	N	0.294	neutral	None	None	None	None	I
H/C	0.119	likely_benign	0.1218	benign	0.367	Stabilizing	0.788	D	0.407	neutral	None	None	None	None	I
H/D	0.4452	ambiguous	0.4404	ambiguous	-0.241	Destabilizing	0.007	N	0.347	neutral	N	0.432844117	None	None	I
H/E	0.3523	ambiguous	0.344	ambiguous	-0.163	Destabilizing	None	N	0.132	neutral	None	None	None	None	I
H/F	0.2636	likely_benign	0.2658	benign	0.737	Stabilizing	0.245	N	0.517	neutral	None	None	None	None	I
H/G	0.3719	ambiguous	0.3465	ambiguous	-0.669	Destabilizing	0.018	N	0.305	neutral	None	None	None	None	I
H/I	0.2329	likely_benign	0.2262	benign	0.631	Stabilizing	0.085	N	0.515	neutral	None	None	None	None	I
H/K	0.1505	likely_benign	0.1484	benign	-0.291	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
H/L	0.1198	likely_benign	0.1155	benign	0.631	Stabilizing	0.014	N	0.323	neutral	N	0.43147868	None	None	I
H/M	0.3626	ambiguous	0.3572	ambiguous	0.435	Stabilizing	0.497	N	0.434	neutral	None	None	None	None	I
H/N	0.17	likely_benign	0.1645	benign	-0.351	Destabilizing	0.014	N	0.341	neutral	N	0.434825629	None	None	I
H/P	0.7919	likely_pathogenic	0.759	pathogenic	0.338	Stabilizing	0.065	N	0.493	neutral	N	0.502493416	None	None	I
H/Q	0.1231	likely_benign	0.1234	benign	-0.131	Destabilizing	0.007	N	0.327	neutral	N	0.406233519	None	None	I
H/R	0.0584	likely_benign	0.0599	benign	-0.903	Destabilizing	None	N	0.107	neutral	N	0.330100964	None	None	I
H/S	0.2703	likely_benign	0.2503	benign	-0.311	Destabilizing	0.018	N	0.313	neutral	None	None	None	None	I
H/T	0.2415	likely_benign	0.2231	benign	-0.128	Destabilizing	0.018	N	0.319	neutral	None	None	None	None	I
H/V	0.1768	likely_benign	0.1749	benign	0.338	Stabilizing	0.044	N	0.414	neutral	None	None	None	None	I
H/W	0.3293	likely_benign	0.3225	benign	0.923	Stabilizing	0.788	D	0.435	neutral	None	None	None	None	I
H/Y	0.1127	likely_benign	0.1124	benign	1.082	Stabilizing	0.065	N	0.449	neutral	N	0.454278182	None	None	I

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.