Submissions for variant NM_021954.4(GJA3):c.151G>C (p.Asp51His)

dbSNP: rs2141138391

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001971221	SCV002266382	likely pathogenic	Cataract 14 multiple types	2021-05-07	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with congenital cataracts (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 51 of the GJA3 protein (p.Asp51His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine.
CeGaT Center for Human Genetics Tuebingen	RCV003312032	SCV004010215	likely pathogenic	not provided	2023-04-01	criteria provided, single submitter	clinical testing	GJA3: PM1, PM2, PP3, PS4:Supporting