TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23993	72202;72203;72204	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
N2AB	22352	67279;67280;67281	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
N2A	21425	64498;64499;64500	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
N2B	14928	45007;45008;45009	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
Novex-1	15053	45382;45383;45384	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
Novex-2	15120	45583;45584;45585	chr2:178574155;178574154;178574153	chr2:179438882;179438881;179438880
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-62
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1244
• 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
A/V	rs2154171336	None	0.022	N	0.103	0.151	0.276898752692	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93648E-04	None	0	0	0	0	0
A/V	rs2154171336	None	0.022	N	0.103	0.151	0.276898752692	gnomAD-4.0.0	6.56883E-06	None	None	None	None	N	None	0	0	None	0	1.94099E-04	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
A/C	0.4094	ambiguous	0.4035	ambiguous	-0.927	Destabilizing	0.998	D	0.453	neutral	None	None	None	None	N
A/D	0.3287	likely_benign	0.341	ambiguous	-1.309	Destabilizing	0.669	D	0.429	neutral	N	0.489660192	None	None	N
A/E	0.2807	likely_benign	0.2802	benign	-1.388	Destabilizing	0.067	N	0.241	neutral	None	None	None	None	N
A/F	0.362	ambiguous	0.387	ambiguous	-1.294	Destabilizing	0.974	D	0.501	neutral	None	None	None	None	N
A/G	0.1544	likely_benign	0.1594	benign	-1.172	Destabilizing	0.801	D	0.349	neutral	N	0.446466775	None	None	N
A/H	0.4817	ambiguous	0.4799	ambiguous	-1.288	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	N
A/I	0.2698	likely_benign	0.2859	benign	-0.592	Destabilizing	0.728	D	0.402	neutral	None	None	None	None	N
A/K	0.4598	ambiguous	0.4609	ambiguous	-1.189	Destabilizing	0.067	N	0.253	neutral	None	None	None	None	N
A/L	0.1997	likely_benign	0.2065	benign	-0.592	Destabilizing	0.525	D	0.385	neutral	None	None	None	None	N
A/M	0.1866	likely_benign	0.1987	benign	-0.38	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	N
A/N	0.2503	likely_benign	0.2623	benign	-0.857	Destabilizing	0.949	D	0.489	neutral	None	None	None	None	N
A/P	0.9411	likely_pathogenic	0.9508	pathogenic	-0.679	Destabilizing	0.966	D	0.485	neutral	N	0.486309942	None	None	N
A/Q	0.3228	likely_benign	0.3106	benign	-1.112	Destabilizing	0.142	N	0.25	neutral	None	None	None	None	N
A/R	0.4327	ambiguous	0.4363	ambiguous	-0.727	Destabilizing	0.728	D	0.458	neutral	None	None	None	None	N
A/S	0.0887	likely_benign	0.0914	benign	-1.15	Destabilizing	0.801	D	0.372	neutral	N	0.425435355	None	None	N
A/T	0.0807	likely_benign	0.0813	benign	-1.146	Destabilizing	0.801	D	0.379	neutral	N	0.407420023	None	None	N
A/V	0.1335	likely_benign	0.141	benign	-0.679	Destabilizing	0.022	N	0.103	neutral	N	0.421184328	None	None	N
A/W	0.8192	likely_pathogenic	0.829	pathogenic	-1.544	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
A/Y	0.4981	ambiguous	0.5075	ambiguous	-1.18	Destabilizing	0.991	D	0.503	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.