TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16069	48430;48431;48432	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
N2AB	14428	43507;43508;43509	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
N2A	13501	40726;40727;40728	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
N2B	7004	21235;21236;21237	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
Novex-1	7129	21610;21611;21612	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
Novex-2	7196	21811;21812;21813	chr2:178616586;178616585;178616584	chr2:179481313;179481312;179481311
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: Fn3-4
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.2875
• 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/E	rs752099554	-0.442	0.012	N	0.287	0.065	0.215109475489	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/E	rs752099554	-0.442	0.012	N	0.287	0.065	0.215109475489	gnomAD-4.0.0	1.59419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86349E-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	0.2801	likely_benign	0.3121	benign	-0.217	Destabilizing	0.016	N	0.399	neutral	None	None	None	None	N
K/C	0.5977	likely_pathogenic	0.6957	pathogenic	-0.257	Destabilizing	0.864	D	0.443	neutral	None	None	None	None	N
K/D	0.5805	likely_pathogenic	0.5983	pathogenic	-0.073	Destabilizing	0.072	N	0.405	neutral	None	None	None	None	N
K/E	0.234	likely_benign	0.2166	benign	-0.065	Destabilizing	0.012	N	0.287	neutral	N	0.476740702	None	None	N
K/F	0.8165	likely_pathogenic	0.8475	pathogenic	-0.422	Destabilizing	0.356	N	0.468	neutral	None	None	None	None	N
K/G	0.3038	likely_benign	0.34	benign	-0.447	Destabilizing	None	N	0.161	neutral	None	None	None	None	N
K/H	0.3222	likely_benign	0.3581	ambiguous	-0.876	Destabilizing	0.356	N	0.425	neutral	None	None	None	None	N
K/I	0.4587	ambiguous	0.5034	ambiguous	0.319	Stabilizing	0.356	N	0.483	neutral	None	None	None	None	N
K/L	0.4323	ambiguous	0.462	ambiguous	0.319	Stabilizing	0.072	N	0.423	neutral	None	None	None	None	N
K/M	0.3214	likely_benign	0.3378	benign	0.371	Stabilizing	0.295	N	0.433	neutral	N	0.506989808	None	None	N
K/N	0.4827	ambiguous	0.4742	ambiguous	0.108	Stabilizing	0.055	N	0.194	neutral	N	0.473645445	None	None	N
K/P	0.4578	ambiguous	0.5039	ambiguous	0.169	Stabilizing	0.136	N	0.444	neutral	None	None	None	None	N
K/Q	0.151	likely_benign	0.1543	benign	-0.172	Destabilizing	0.001	N	0.115	neutral	N	0.480326657	None	None	N
K/R	0.0628	likely_benign	0.0626	benign	-0.135	Destabilizing	None	N	0.062	neutral	N	0.449508273	None	None	N
K/S	0.3738	ambiguous	0.3944	ambiguous	-0.456	Destabilizing	0.016	N	0.228	neutral	None	None	None	None	N
K/T	0.227	likely_benign	0.2405	benign	-0.292	Destabilizing	0.055	N	0.373	neutral	N	0.467693225	None	None	N
K/V	0.3867	ambiguous	0.4204	ambiguous	0.169	Stabilizing	0.072	N	0.463	neutral	None	None	None	None	N
K/W	0.6622	likely_pathogenic	0.7322	pathogenic	-0.337	Destabilizing	0.864	D	0.467	neutral	None	None	None	None	N
K/Y	0.6627	likely_pathogenic	0.6855	pathogenic	0.012	Stabilizing	0.356	N	0.439	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.