ClinVar Miner

Submissions for variant NM_005267.5(GJA8):c.262C>G (p.Pro88Ala)

dbSNP: rs80358200
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805199 SCV000945146 pathogenic Cataract 1 multiple types 2019-01-18 criteria provided, single submitter clinical testing This variant disrupts the p.Pro88 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been observed in individuals with GJA8-related conditions (PMID: 9497259, 19073179, 12800976, 18587493, 16397066, 24535056), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as 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 to be de novo in an individual affected with bilateral cataract (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 88 of the GJA8 protein (p.Pro88Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.
CeGaT Center for Human Genetics Tuebingen RCV003886442 SCV004704290 likely pathogenic not provided 2024-01-01 criteria provided, single submitter clinical testing GJA8: PM1, PM2, PM5, PM6:Supporting, PP3, PS4:Supporting

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