TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16973	51142;51143;51144	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
N2AB	15332	46219;46220;46221	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
N2A	14405	43438;43439;43440	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
N2B	7908	23947;23948;23949	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
Novex-1	8033	24322;24323;24324	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
Novex-2	8100	24523;24524;24525	chr2:178611212;178611211;178611210	chr2:179475939;179475938;179475937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-111
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4431
• 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
S/G	rs943563172	None	0.012	N	0.501	0.063	0.117506650769	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
S/N	None	None	None	N	0.283	0.035	0.0551355673512	gnomAD-4.0.0	6.84671E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65859E-05

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
S/A	0.0856	likely_benign	0.0835	benign	-0.367	Destabilizing	0.016	N	0.46	neutral	None	None	None	None	N
S/C	0.0878	likely_benign	0.0812	benign	-0.407	Destabilizing	0.828	D	0.548	neutral	N	0.453019841	None	None	N
S/D	0.2631	likely_benign	0.2127	benign	0.037	Stabilizing	0.038	N	0.499	neutral	None	None	None	None	N
S/E	0.3335	likely_benign	0.275	benign	0.067	Stabilizing	0.016	N	0.498	neutral	None	None	None	None	N
S/F	0.1785	likely_benign	0.1655	benign	-0.503	Destabilizing	0.356	N	0.577	neutral	None	None	None	None	N
S/G	0.112	likely_benign	0.1007	benign	-0.636	Destabilizing	0.012	N	0.501	neutral	N	0.449232792	None	None	N
S/H	0.1599	likely_benign	0.1372	benign	-1.037	Destabilizing	None	N	0.329	neutral	None	None	None	None	N
S/I	0.1013	likely_benign	0.0947	benign	0.237	Stabilizing	0.171	N	0.592	neutral	N	0.43071254	None	None	N
S/K	0.3832	ambiguous	0.3157	benign	-0.52	Destabilizing	0.016	N	0.506	neutral	None	None	None	None	N
S/L	0.1019	likely_benign	0.1	benign	0.237	Stabilizing	0.038	N	0.532	neutral	None	None	None	None	N
S/M	0.1579	likely_benign	0.1506	benign	0.125	Stabilizing	0.628	D	0.567	neutral	None	None	None	None	N
S/N	0.0806	likely_benign	0.0776	benign	-0.576	Destabilizing	None	N	0.283	neutral	N	0.416117381	None	None	N
S/P	0.6491	likely_pathogenic	0.602	pathogenic	0.072	Stabilizing	0.356	N	0.592	neutral	None	None	None	None	N
S/Q	0.284	likely_benign	0.2371	benign	-0.569	Destabilizing	0.072	N	0.515	neutral	None	None	None	None	N
S/R	0.3112	likely_benign	0.2328	benign	-0.524	Destabilizing	None	N	0.379	neutral	N	0.40138121	None	None	N
S/T	0.0679	likely_benign	0.0669	benign	-0.52	Destabilizing	0.001	N	0.265	neutral	N	0.406868714	None	None	N
S/V	0.1272	likely_benign	0.116	benign	0.072	Stabilizing	0.038	N	0.545	neutral	None	None	None	None	N
S/W	0.2809	likely_benign	0.2379	benign	-0.606	Destabilizing	0.864	D	0.593	neutral	None	None	None	None	N
S/Y	0.1401	likely_benign	0.1316	benign	-0.27	Destabilizing	0.214	N	0.591	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.