TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29352	88279;88280;88281	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
N2AB	27711	83356;83357;83358	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
N2A	26784	80575;80576;80577	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
N2B	20287	61084;61085;61086	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
Novex-1	20412	61459;61460;61461	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
Novex-2	20479	61660;61661;61662	chr2:178557100;178557099;178557098	chr2:179421827;179421826;179421825
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-102
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0974
• 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
V/I	None	None	None	N	0.176	0.086	0.199424873507	gnomAD-4.0.0	6.84282E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99486E-07	0	0
V/L	None	None	None	N	0.303	0.233	0.183819452728	gnomAD-4.0.0	6.84282E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99486E-07	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
V/A	0.4786	ambiguous	0.3391	benign	-2.078	Highly Destabilizing	None	N	0.357	neutral	N	0.455024232	None	None	N
V/C	0.8671	likely_pathogenic	0.82	pathogenic	-2.049	Highly Destabilizing	0.824	D	0.765	deleterious	None	None	None	None	N
V/D	0.9939	likely_pathogenic	0.9908	pathogenic	-2.473	Highly Destabilizing	0.317	N	0.813	deleterious	D	0.542372864	None	None	N
V/E	0.9847	likely_pathogenic	0.9776	pathogenic	-2.159	Highly Destabilizing	0.38	N	0.791	deleterious	None	None	None	None	N
V/F	0.6401	likely_pathogenic	0.5356	ambiguous	-1.292	Destabilizing	0.317	N	0.809	deleterious	N	0.51460737	None	None	N
V/G	0.8115	likely_pathogenic	0.7277	pathogenic	-2.702	Highly Destabilizing	0.062	N	0.759	deleterious	N	0.515874818	None	None	N
V/H	0.9922	likely_pathogenic	0.9884	pathogenic	-2.643	Highly Destabilizing	0.935	D	0.775	deleterious	None	None	None	None	N
V/I	0.0828	likely_benign	0.0818	benign	-0.281	Destabilizing	None	N	0.176	neutral	N	0.478565259	None	None	N
V/K	0.9853	likely_pathogenic	0.9815	pathogenic	-1.582	Destabilizing	0.38	N	0.79	deleterious	None	None	None	None	N
V/L	0.3562	ambiguous	0.2894	benign	-0.281	Destabilizing	None	N	0.303	neutral	N	0.46511309	None	None	N
V/M	0.3933	ambiguous	0.3175	benign	-0.75	Destabilizing	0.38	N	0.619	neutral	None	None	None	None	N
V/N	0.9773	likely_pathogenic	0.9644	pathogenic	-2.18	Highly Destabilizing	0.555	D	0.809	deleterious	None	None	None	None	N
V/P	0.9908	likely_pathogenic	0.9866	pathogenic	-0.858	Destabilizing	0.38	N	0.807	deleterious	None	None	None	None	N
V/Q	0.9753	likely_pathogenic	0.966	pathogenic	-1.805	Destabilizing	0.555	D	0.774	deleterious	None	None	None	None	N
V/R	0.9694	likely_pathogenic	0.9611	pathogenic	-1.805	Destabilizing	0.38	N	0.813	deleterious	None	None	None	None	N
V/S	0.8743	likely_pathogenic	0.803	pathogenic	-2.862	Highly Destabilizing	0.081	N	0.764	deleterious	None	None	None	None	N
V/T	0.7532	likely_pathogenic	0.6547	pathogenic	-2.36	Highly Destabilizing	0.081	N	0.659	neutral	None	None	None	None	N
V/W	0.9942	likely_pathogenic	0.9899	pathogenic	-1.717	Destabilizing	0.935	D	0.769	deleterious	None	None	None	None	N
V/Y	0.9619	likely_pathogenic	0.943	pathogenic	-1.366	Destabilizing	0.555	D	0.807	deleterious	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.