ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.2242G>A (p.Gly748Ser)

gnomAD frequency: 0.00002  dbSNP: rs762139460
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV000673217 SCV000893588 likely pathogenic Autosomal recessive Alport syndrome 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV001333199 SCV001525715 uncertain significance Benign familial hematuria 2018-09-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. The c.2242G>A (p.G748S) variant was previously reported as heterozygous (without second allele) in five individuals from two unrelated families with familial microhematuria with or without focal segmental glomerulosclerosis [PMID 28632965]
Myriad Genetics, Inc. RCV000673217 SCV002060392 uncertain significance Autosomal recessive Alport syndrome 2021-11-03 criteria provided, single submitter clinical testing NM_000092.4(COL4A4):c.2242G>A(G748S) is a missense variant classified as a variant of uncertain significance in the context of COL4A4-related Alport syndrome. G748S has not been observed in cases with relevant disease. Functional assessments of this variant are not available in the literature. G748S has been observed in population frequency databases (gnomAD: ASJ 0.01%). In summary, there is insufficient evidence to classify NM_000092.4(COL4A4):c.2242G>A(G748S) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV001855593 SCV002230436 pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 748 of the COL4A4 protein (p.Gly748Ser). This variant is present in population databases (rs762139460, gnomAD 0.01%). This missense change has been observed in individuals with COL4A4-related conditions (PMID: 28632965). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 557121). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A4 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001855593 SCV002762423 uncertain significance not provided 2022-06-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene; This variant is associated with the following publications: (PMID: 31589614, 28632965, 33391746)
CeGaT Center for Human Genetics Tuebingen RCV001855593 SCV003916251 likely pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing COL4A4: PM1:Strong, PM2, PP1, PP3, PP4

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